Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.
Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.
Subset of helper-effector T-lymphocytes which synthesize and secrete IL-17, IL-17F, and IL-22. These cytokines are involved in host defenses and tissue inflammation in autoimmune diseases.
Homeostatic control of the immune system by secretion of different cytokines by the Th1 and Th2 cells. The concentration dependent binding of the various cytokines to specific receptors determines the balance (or imbalance leading to disease).
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.
Time period from 1801 through 1900 of the common era.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Time period from 1601 through 1700 of the common era.
Inbred BALB/c mice are a strain of laboratory mice that have been selectively bred to be genetically identical to each other, making them useful for scientific research and experiments due to their consistent genetic background and predictable responses to various stimuli or treatments.
Time period from 1901 through 2000 of the common era.
Time period from 1701 through 1800 of the common era.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
Time period from 1401 through 1500 of the common era.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
Time period from 1501 through 1600 of the common era.
A GATA transcription factor that is found predominately in LYMPHOID CELL precursors and has been implicated in the CELL DIFFERENTIATION of HELPER T-CELLS. Haploinsufficiency of GATA3 is associated with HYPOPARATHYROIDISM; SENSORINEURAL HEARING LOSS; and renal anomalies syndrome.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC
Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
An orphan nuclear receptor found in the THYMUS where it plays a role in regulating the development and maturation of thymocytes. An isoform of this protein, referred to as RORgammaT, is produced by an alternatively transcribed mRNA.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A cytokine synthesized by T-LYMPHOCYTES that produces proliferation, immunoglobulin isotype switching, and immunoglobulin production by immature B-LYMPHOCYTES. It appears to play a role in regulating inflammatory and immune responses.
A cytokine that promotes differentiation and activation of EOSINOPHILS. It also triggers activated B-LYMPHOCYTES to differentiate into IMMUNOGLOBULIN-secreting cells.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-23 is comprised of a unique 19 kDa subunit and 40 kDa subunit that is shared with INTERLEUKIN-12. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells
Proteins containing a region of conserved sequence, about 200 amino acids long, which encodes a particular sequence specific DNA binding domain (the T-box domain). These proteins are transcription factors that control developmental pathways. The prototype of this family is the mouse Brachyury (or T) gene product.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
An encapsulated lymphatic organ through which venous blood filters.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-4. Stat6 has been shown to partner with NF-KAPPA B and CCAAT-ENHANCER-BINDING PROTEINS to regulate GENETIC TRANSCRIPTION of interleukin-4 responsive GENES.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-12 in T-LYMPHOCYTES. Stat4 is an important signaling molecule for differentiation in TH1 CELLS.
An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5)
Antigen-type substances that produce immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).

Reciprocal control of T helper cell and dendritic cell differentiation. (1/5141)

It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (TH1) or TH2 cells. Human monocyte (pDC1)-derived dendritic cells (DC1) were found to induce TH1 differentiation, whereas dendritic cells (DC2) derived from CD4+CD3-CD11c- plasmacytoid cells (pDC2) induced TH2 differentiation by use of a mechanism unaffected by interleukin-4 (IL-4) or IL-12. The TH2 cytokine IL-4 enhanced DC1 maturation and killed pDC2, an effect potentiated by IL-10 but blocked by CD40 ligand and interferon-gamma. Thus, a negative feedback loop from the mature T helper cells may selectively inhibit prolonged TH1 or TH2 responses by regulating survival of the appropriate dendritic cell subset.  (+info)

Enhanced Th1 and dampened Th2 responses synergize to inhibit acute granulomatous and fibrotic responses in murine schistosomiasis mansoni. (2/5141)

In murine schistosomiasis mansoni, CD4(+) Th1 and Th2 cells participate in the ovum-induced granulomatous inflammation. Previous studies showed that the interleukin-12 (IL-12)-induced Th1 response strongly suppressed the Th2-cell-mediated pulmonary granuloma development in naive or primed mice. However, liver granulomas were only moderately suppressed in egg-vaccinated, recombinant IL-12 (rIL-12)-treated infected mice. The present study shows that repeated rIL-12 injections given during early granuloma development at 5 to 7 weeks after infection prolonged the Th1 phase and resulted in gamma interferon-mediated suppression of liver granulomas. The timing is crucial: if given at 6 to 8 weeks, during the Th2-dominated phase of florid granuloma growth, the treatment is ineffective. Daily injections of rIL-12 given between 5 and 7.5 weeks during the period of granuloma growth achieved a somewhat-stronger diminution in granuloma growth with less deposition of collagen but caused 60% mortality and liver pathology. In contrast, combined treatment with rIL-12 and anti-IL-4-anti-IL-10 monoclonal antibody (MAb) injections given during the Th2 phase strongly inhibited liver granuloma growth without mortality. The diminished inflammatory response was accompanied by less deposition of collagen in the liver. Moreover, neutralization of endogenous IL-12 by anti-IL-12 MAbs effectively decreased the early Th1 phase (between 5 and 6 weeks after infection) but not the developing Th2 phase (5 to 7 weeks) of granuloma development. These studies indicate that the granulomatous response in infected mice can be manipulated by utilizing the Th1-Th2-subset antagonism with potential salutary results in the amelioration of fibrous pathology.  (+info)

Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1. (3/5141)

Interleukin-10 (IL-10) helps maintain polarized T-helper cells in a T-helper lymphocyte 2 (Th2) phenotype. Part of this process involves the prevention of the development of Th1 cells, which are a primary source of interferon gamma (IFNgamma), a potent activator of monocytes and an inhibitor of Th2 proliferation. Because monocytes and macrophages are important mediators of Th1-type responses, such as delayed-type hypersensitivity, we sought to determine if IL-10 could directly mediate inhibition of IFNgamma- and IFNalpha-induced gene expression in these cells. Highly purified monocytes were incubated with IL-10 for 60 to 90 minutes before the addition of IFNgamma or IFNalpha. IL-10 preincubation resulted in the inhibition of gene expression for several IFN-induced genes, such as IP-10, ISG54, and intercellular adhesion molecule-1. The reduction in gene expression resulted from the ability of IL-10 to suppress IFN-induced assembly of signal transducer and activator of transcription (STAT) factors to specific promoter motifs on IFNalpha- and IFNgamma-inducible genes. This was accomplished by preventing the IFN-induced tyrosine phosphorylation of STAT1, a component of both IFNalpha- and IFNgamma-induced DNA binding complexes. Therefore, IL-10 can directly inhibit STAT-dependent early response gene expression induced by both IFNalpha and IFNgamma in monocytes by suppressing the tyrosine phosphorylation of STAT1. This may occur through the ability of IL-10 to induce expression of the gene, suppressor of cytokine signaling 3 (SOCS3).  (+info)

Cytokine network and resident renal cells in glomerular diseases. (4/5141)

This review has highlighted the cytokine network which is involved in renal damage from an initial, even transient, stage to extensive glomerular and tubulointerstitial sclerosis. Studies of a variety of different proliferative glomerulonephritides have documented the prominent role of macrophages in infiltrating mesangium, subendothelial area and crescentic formation. Thus, they stimulate crescent glomerular cells to produce other cytokines and growth factors. The identification of other mediators, released by the monocytes in the interstitium, exemplifies the important role of these cells in progressive interstitial scarring through the release of fibrogenic cytokines. In addition, renal tubular cells have been found to produce a vast array of cytokines and growth factors which participate in the generation of renal interstitial scarring.  (+info)

Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. (5/5141)

Helper T cells are classified into Th1 and Th2 subsets based on their profiles of cytokine production. Th1 cells are involved in cell-mediated immunity, whereas Th2 cells induce humoral responses. Selective recruitment of these two subsets depends on specific adhesion molecules and specific chemoattractants. Here, we demonstrate that the T cell-directed CC chemokine thymus and activation-regulated chemokine (TARC) was abundantly produced by monocytes treated with granulocyte macrophage colony stimulating factor (GM-CSF) or IL-3, especially in the presence of IL-4 and by dendritic cells derived from monocytes cultured with GM-CSF + IL-4. The receptor for TARC and another macrophage/dendritic cell-derived CC chemokine macrophage-derived chemokine (MDC) is CCR4, a G protein-coupled receptor. CCR4 was found to be expressed on approximately 20% of adult peripheral blood effector/memory CD4+ T cells. T cells attracted by TARC and MDC generated cell lines predominantly producing Th2-type cytokines, IL-4 and IL-5. Fractionated CCR4+ cells but not CCR4- cells also selectively gave rise to Th2-type cell lines. When naive CD4+ T cells from adult peripheral blood were polarized in vitro, Th2-type cells selectively expressed CCR4 and vigorously migrated toward TARC and MDC. Taken together, CCR4 is selectively expressed on Th2-type T cells and antigen-presenting cells may recruit Th2 cells expressing CCR4 by producing TARC and MDC in Th2-dominant conditions.  (+info)

Patterns of A2A extracellular adenosine receptor expression in different functional subsets of human peripheral T cells. Flow cytometry studies with anti-A2A receptor monoclonal antibodies. (6/5141)

Signaling through A2A adenosine receptors (A2AR) regulates T lymphocyte expansion and modulates T cell receptor (TCR)-mediated effector functions in vitro. To understand the role of A2ARs in the regulation of immune response, we investigated the expression levels of this receptor in different functional lymphocyte subsets. Monoclonal anti-A2AR antibody was used to develop a flow cytometric assay to quantify the expression A2ARs on lymphocytes. We report that detectable levels of expression of A2ARs are much higher among T cells than B cells. More CD4(+) than CD8(+) T cells express A2ARs, but activation of T cells increases A2AR expression, predominantly in CD8(+) T cells. No significant differences were found in the proportion of A2AR+ cells between CD8(low) and CD8(high) T cells or between TCR/CD3(low) and TCR/CD3(high) T cells. Studies of T helper cell subsets (TH1 and TH2) reveal that lymphokine-producing cells are much more likely to express A2ARs than are cells that do not produce lymphokines. These results suggest that A2ARs are variably expressed on T cell subsets and may regulate cytokine production in activated T lymphocytes.  (+info)

Effect of renal dialysis therapy modality on T cell cytokine production. (7/5141)

INTRODUCTION: Dialysis has been associated with acute changes in the complement activation status, granulocyte markers, macrophage function, T cell activation and the release of pro-inflammatory cytokines. The most common analysis of cytokine production in patients on dialysis has focused on the changes in monokines (particularly IL-1 and TNF alpha), however it is becoming clear that T cell cytokines play a major role in the impaired lymphocyte function of dialysis patients. METHODS: To assess the effect of dialysis modality on T cell function we analysed the ability of T cells within peripheral blood mononuclear cell populations (PBMC) to produce cytokines after mitogen (phorbol-12-myristate-13-acetate; PMA and lonomycin; I) stimulation in patients on peritoneal dialysis (PD) compared to low flux haemodialysis (HD) and normal individuals (controls). RESULTS: In control PBMC, PMA + I stimulation significantly increased the percentage of CD3+ cells expressing IL-2, IFN gamma, TNF alpha, IL-4 and IL-10, as expected. However, although mitogen stimulation significantly enhanced the percentage of the classical Th1 cytokines (IL-2, IFN gamma and TNF alpha) in the low flux HD PBMC, it had no effect on CD3+ IL-2 or CD3+ TNF alpha producing cells in the PD group. In contrast, the percentage of T cells producing Th2 cytokines (IL-4 and IL-10) could not be consistently enhanced by mitogen in either dialysis group. CONCLUSIONS: We suggest that PD alters the ability of T cells to produce cytokines, possibly by causing an 'exhaustion' of the Th1 cells, thereby preventing cells to produce cytokine on ex vivo stimulation. Furthermore, since T cells from both low flux HD and PD groups could not be induced to produce Th2 cytokines we suggest that uraemia or dialysis per se inhibits T cells from producing Th2 cytokines.  (+info)

Marking IL-4-producing cells by knock-in of the IL-4 gene. (8/5141)

IL-4 is a cytokine which can be expressed by a number of cell types including Th2 cells, mast cells and a population of CD4+ NK1.1+ NK T cells. Although phenotypic markers exist for identifying each of these cell types, there is at present no known cell surface marker common to all IL-4-producing cells. Using gene targeting in embryonic stem cells, we have modified the IL-4 locus by knock-in of a transmembrane domain to generate mice that express a membrane-bound form of IL-4 (mIL-4). Flow cytometry using an IL-4-specific mAb allowed the detection of IL-secreting Th2 cells, mast cells and NK T cells from mIL-4 mice. Furthermore, the analysis of immune responses in mIL-4 mice following immunization with anti-CD3 and anti-IgD has allowed us to identify distinct subpopulations of IL-4-producing NK T cells. Thus, the expression of IL-4 in a membrane-bound form provides a novel method for the identification and characterization of IL-4-producing cells.  (+info)

Th2 cells, or T helper 2 cells, are a type of CD4+ T cell that plays a key role in the immune response to parasites and allergens. They produce cytokines such as IL-4, IL-5, IL-13 which promote the activation and proliferation of eosinophils, mast cells, and B cells, leading to the production of antibodies such as IgE. Th2 cells also play a role in the pathogenesis of allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis.

It's important to note that an imbalance in Th1/Th2 response can lead to immune dysregulation and disease states. For example, an overactive Th2 response can lead to allergic reactions while an underactive Th2 response can lead to decreased ability to fight off parasitic infections.

It's also worth noting that there are other subsets of CD4+ T cells such as Th1, Th17, Treg and others, each with their own specific functions and cytokine production profiles.

Th1 cells, or Type 1 T helper cells, are a subset of CD4+ T cells that play a crucial role in the cell-mediated immune response. They are characterized by the production of specific cytokines, such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2). Th1 cells are essential for protecting against intracellular pathogens, including viruses, bacteria, and parasites. They activate macrophages to destroy ingested microorganisms, stimulate the differentiation of B cells into plasma cells that produce antibodies, and recruit other immune cells to the site of infection. Dysregulation of Th1 cell responses has been implicated in various autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and type 1 diabetes.

T helper 17 (Th17) cells are a subset of CD4+ T cells, which are a type of white blood cell that plays a crucial role in the immune response. Th17 cells are characterized by their production of certain cytokines, including interleukin-17 (IL-17), IL-21, and IL-22. They are involved in the inflammatory response and play a key role in protecting the body against extracellular bacteria and fungi. However, an overactive Th17 response has been implicated in several autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and psoriasis. Therefore, understanding the regulation of Th17 cells is important for developing new therapies to treat these conditions.

Th1-Th2 balance refers to the regulation of the immune response by two subsets of T helper cells, Th1 and Th2. These cell types produce different cytokines that mediate distinct types of immune responses. A balanced Th1-Th2 response is critical for maintaining immune homeostasis and protecting the body against various pathogens.

Th1 cells primarily mediate cell-mediated immunity, which involves activating macrophages, natural killer (NK) cells, and cytotoxic T lymphocytes (CTLs) to eliminate intracellular pathogens such as viruses and bacteria. Th1 cells produce cytokines like interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2).

Th2 cells, on the other hand, mediate humoral immunity, which involves activating B cells to produce antibodies against extracellular pathogens like parasites and toxins. Th2 cells produce cytokines like interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), and interleukin-13 (IL-13).

An imbalance in the Th1-Th2 response can lead to various immune-related disorders. For example, an overactive Th1 response can result in autoimmune diseases, while an overactive Th2 response can contribute to allergic and atopic conditions like asthma and eczema. Therefore, maintaining a balanced Th1-Th2 response is crucial for optimal immune function and overall health.

Interleukin-4 (IL-4) is a type of cytokine, which is a cell signaling molecule that mediates communication between cells in the immune system. Specifically, IL-4 is produced by activated T cells and mast cells, among other cells, and plays an important role in the differentiation and activation of immune cells called Th2 cells.

Th2 cells are involved in the immune response to parasites, as well as in allergic reactions. IL-4 also promotes the growth and survival of B cells, which produce antibodies, and helps to regulate the production of certain types of antibodies. In addition, IL-4 has anti-inflammatory effects and can help to downregulate the immune response in some contexts.

Defects in IL-4 signaling have been implicated in a number of diseases, including asthma, allergies, and certain types of cancer.

Interleukin-17 (IL-17) is a type of cytokine, which are proteins that play a crucial role in cell signaling and communication during the immune response. IL-17 is primarily produced by a subset of T helper cells called Th17 cells, although other cell types like neutrophils, mast cells, natural killer cells, and innate lymphoid cells can also produce it.

IL-17 has several functions in the immune system, including:

1. Promoting inflammation: IL-17 stimulates the production of various proinflammatory cytokines, chemokines, and enzymes from different cell types, leading to the recruitment of immune cells like neutrophils to the site of infection or injury.
2. Defending against extracellular pathogens: IL-17 plays a critical role in protecting the body against bacterial and fungal infections by enhancing the recruitment and activation of neutrophils, which can engulf and destroy these microorganisms.
3. Regulating tissue homeostasis: IL-17 helps maintain the balance between immune tolerance and immunity in various tissues by regulating the survival, proliferation, and differentiation of epithelial cells, fibroblasts, and other structural components.

However, dysregulated IL-17 production or signaling has been implicated in several inflammatory and autoimmune diseases, such as psoriasis, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Therefore, targeting the IL-17 pathway with specific therapeutics has emerged as a promising strategy for treating these conditions.

Cytokines are a broad and diverse category of small signaling proteins that are secreted by various cells, including immune cells, in response to different stimuli. They play crucial roles in regulating the immune response, inflammation, hematopoiesis, and cellular communication.

Cytokines mediate their effects by binding to specific receptors on the surface of target cells, which triggers intracellular signaling pathways that ultimately result in changes in gene expression, cell behavior, and function. Some key functions of cytokines include:

1. Regulating the activation, differentiation, and proliferation of immune cells such as T cells, B cells, natural killer (NK) cells, and macrophages.
2. Coordinating the inflammatory response by recruiting immune cells to sites of infection or tissue damage and modulating their effector functions.
3. Regulating hematopoiesis, the process of blood cell formation in the bone marrow, by controlling the proliferation, differentiation, and survival of hematopoietic stem and progenitor cells.
4. Modulating the development and function of the nervous system, including neuroinflammation, neuroprotection, and neuroregeneration.

Cytokines can be classified into several categories based on their structure, function, or cellular origin. Some common types of cytokines include interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), chemokines, colony-stimulating factors (CSFs), and transforming growth factors (TGFs). Dysregulation of cytokine production and signaling has been implicated in various pathological conditions, such as autoimmune diseases, chronic inflammation, cancer, and neurodegenerative disorders.

T-lymphocytes, also known as T-cells, are a type of white blood cell that plays a key role in the immune response. They help to protect the body from infection and disease by identifying and attacking foreign substances such as viruses and bacteria.

Helper-inducer T-lymphocytes, also known as CD4+ T-cells or Th0 cells, are a specific subset of T-lymphocytes that help to coordinate the immune response. They do this by activating other immune cells, such as B-lymphocytes (which produce antibodies) and cytotoxic T-lymphocytes (which directly attack infected cells). Helper-inducer T-lymphocytes also release cytokines, which are signaling molecules that help to regulate the immune response.

Helper-inducer T-lymphocytes can differentiate into different subsets of T-cells, depending on the type of cytokines they are exposed to. For example, they can differentiate into Th1 cells, which produce cytokines that help to activate cytotoxic T-lymphocytes and macrophages; or Th2 cells, which produce cytokines that help to activate B-lymphocytes and eosinophils.

It is important to note that helper-inducer T-lymphocytes play a crucial role in the immune response, and dysfunction of these cells can lead to immunodeficiency or autoimmune disorders.

"History, 19th Century" is not a medical term or concept. It refers to the historical events, developments, and figures related to the 1800s in various fields, including politics, culture, science, and technology. However, if you are looking for medical advancements during the 19th century, here's a brief overview:

The 19th century was a period of significant progress in medicine, with numerous discoveries and innovations that shaped modern medical practices. Some notable developments include:

1. Edward Jenner's smallpox vaccine (1796): Although not strictly within the 19th century, Jenner's discovery laid the foundation for vaccination as a preventive measure against infectious diseases.
2. Germ theory of disease: The work of Louis Pasteur, Robert Koch, and others established that many diseases were caused by microorganisms, leading to the development of antiseptic practices and vaccines.
3. Anesthesia: In 1842, Crawford Long first used ether as an anesthetic during surgery, followed by the introduction of chloroform in 1847 by James Simpson.
4. Antisepsis and asepsis: Joseph Lister introduced antiseptic practices in surgery, significantly reducing postoperative infections. Later, the concept of asepsis (sterilization) was developed to prevent contamination during surgical procedures.
5. Microbiology: The development of techniques for culturing and staining bacteria allowed for better understanding and identification of pathogens.
6. Physiology: Claude Bernard's work on the regulation of internal body functions, or homeostasis, contributed significantly to our understanding of human physiology.
7. Neurology: Jean-Martin Charcot made significant contributions to the study of neurological disorders, including multiple sclerosis and Parkinson's disease.
8. Psychiatry: Sigmund Freud developed psychoanalysis, a new approach to understanding mental illnesses.
9. Public health: The 19th century saw the establishment of public health organizations and initiatives aimed at improving sanitation, water quality, and vaccination programs.
10. Medical education reforms: The Flexner Report in 1910 led to significant improvements in medical education standards and practices.

Interferon-gamma (IFN-γ) is a soluble cytokine that is primarily produced by the activation of natural killer (NK) cells and T lymphocytes, especially CD4+ Th1 cells and CD8+ cytotoxic T cells. It plays a crucial role in the regulation of the immune response against viral and intracellular bacterial infections, as well as tumor cells. IFN-γ has several functions, including activating macrophages to enhance their microbicidal activity, increasing the presentation of major histocompatibility complex (MHC) class I and II molecules on antigen-presenting cells, stimulating the proliferation and differentiation of T cells and NK cells, and inducing the production of other cytokines and chemokines. Additionally, IFN-γ has direct antiproliferative effects on certain types of tumor cells and can enhance the cytotoxic activity of immune cells against infected or malignant cells.

I believe there might be a bit of confusion in your question. A "history" in medical terms usually refers to the detailed account of a patient's symptoms, illnesses, and treatments received, which is used by healthcare professionals to understand their health status and provide appropriate care. It is not typically associated with a specific century like the 17th century.

If you are asking for information about the medical practices or significant developments in the field of medicine during the 17th century, I would be happy to provide some insight into that. The 17th century was a time of great advancement in medical knowledge and practice, with several key figures and events shaping the course of medical history.

Some notable developments in medicine during the 17th century include:

1. William Harvey's discovery of the circulation of blood (1628): English physician William Harvey published his groundbreaking work "De Motu Cordis" (On the Motion of the Heart and Blood), which described the circulatory system and the role of the heart in pumping blood throughout the body. This discovery fundamentally changed our understanding of human anatomy and physiology.
2. The development of the microscope (1600s): The invention of the microscope allowed scientists to observe structures that were previously invisible to the naked eye, such as cells, bacteria, and other microorganisms. This technology opened up new avenues of research in anatomy, physiology, and pathology, paving the way for modern medical science.
3. The establishment of the Royal Society (1660): The Royal Society, a prominent scientific organization in the UK, was founded during this century to promote scientific inquiry and share knowledge among its members. Many notable scientists and physicians, including Robert Hooke and Christopher Wren, were part of the society and contributed significantly to the advancement of medical science.
4. The Smallpox Vaccination (1796): Although this occurred near the end of the 18th century, the groundwork for Edward Jenner's smallpox vaccine was laid during the 17th century. Smallpox was a significant public health issue during this time, and Jenner's development of an effective vaccine marked a major milestone in the history of medicine and public health.
5. The work of Sylvius de le Boe (1614-1672): A Dutch physician and scientist, Sylvius de le Boe made significant contributions to our understanding of human anatomy and physiology. He was the first to describe the circulation of blood in the lungs and identified the role of the liver in metabolism.

These are just a few examples of the many advancements that took place during the 17th century, shaping the course of medical history and laying the foundation for modern medicine.

BALB/c is an inbred strain of laboratory mouse that is widely used in biomedical research. The strain was developed at the Institute of Cancer Research in London by Henry Baldwin and his colleagues in the 1920s, and it has since become one of the most commonly used inbred strains in the world.

BALB/c mice are characterized by their black coat color, which is determined by a recessive allele at the tyrosinase locus. They are also known for their docile and friendly temperament, making them easy to handle and work with in the laboratory.

One of the key features of BALB/c mice that makes them useful for research is their susceptibility to certain types of tumors and immune responses. For example, they are highly susceptible to developing mammary tumors, which can be induced by chemical carcinogens or viral infection. They also have a strong Th2-biased immune response, which makes them useful models for studying allergic diseases and asthma.

BALB/c mice are also commonly used in studies of genetics, neuroscience, behavior, and infectious diseases. Because they are an inbred strain, they have a uniform genetic background, which makes it easier to control for genetic factors in experiments. Additionally, because they have been bred in the laboratory for many generations, they are highly standardized and reproducible, making them ideal subjects for scientific research.

I'm sorry for any confusion, but "History, 20th Century" is a broad and complex topic that refers to the events, developments, and transformations that occurred throughout the world during the 1900s. It is not a medical term or concept. If you're interested in learning more about this historical period, I would recommend consulting a history textbook, reputable online resources, or speaking with a historian. They can provide detailed information about the political, social, economic, and cultural changes that took place during the 20th century.

I believe there might be a bit of confusion in your question. A "history" in medical terms usually refers to the detailed account of a patient's symptoms, illnesses, and treatments received, which is used by healthcare professionals to understand their health status and provide appropriate care. It is not typically associated with a specific century like the 18th century.

If you are asking for information about the medical practices or significant developments in the field of medicine during the 18th century, I would be happy to provide some insight into that! The 18th century was a time of great advancement and change in the medical field, with many notable discoveries and innovations. Some examples include:

* The development of smallpox vaccination by Edward Jenner in 1796
* The discovery of oxygen by Joseph Priestley in 1774
* The invention of the thermometer by Gabriel Fahrenheit in 1714
* The publication of "An Inquiry into the Causes and Effects of the Variolae Vaccinae" by Edward Jenner in 1798, which helped to establish the concept of vaccination
* The founding of the Royal Society of Medicine in London in 1773
* The development of new surgical techniques and instruments, such as the use of tourniquets and catgut sutures.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

I believe there might be a bit of confusion in your question. A "medical definition" refers to the explanation of a medical term or concept. On the other hand, "15th century" is a historical time period and does not have a medical definition per se. However, I can provide you with some context regarding the medical advancements and practices during the 15th century.

The 15th century was marked by significant developments in medicine, particularly in Europe, as it transitioned from medieval to early modern medicine. Some key aspects of 15th-century medicine include:

1. Universities and medical education: Universities became more prominent centers for medical education, with institutions like the University of Bologna, Padua, Montpellier, and Salamanca playing crucial roles in shaping medical thought. Medical faculties taught subjects such as anatomy, physiology, pathology, surgery, and pharmacology based on ancient Greek and Roman texts, mainly Galen and Hippocrates.

2. Anatomical studies: The 15th century saw the beginning of a more accurate understanding of human anatomy. Italian anatomist and physician Mondino de Luzzi (c. 1270–1326) is known for his influential anatomy textbook, "Anathomia," which was widely used during this period. Later in the century, Andreas Vesalius (1514–1564), often regarded as the founder of modern human anatomy, began his groundbreaking work on detailed dissections and accurate representations of the human body.

3. Renaissance of medical illustrations: The 15th century marked a revival in medical illustrations, with artists like Leonardo da Vinci (1452–1519) creating highly accurate anatomical drawings based on dissections. These detailed images helped physicians better understand the human body and its functions.

4. Development of hospitals: Hospitals during this time became more organized and specialized, focusing on specific medical conditions or patient populations. For example, mental health institutions, known as "madhouses" or "asylums," were established to treat individuals with mental illnesses.

5. Plague and public health: The ongoing threat of the bubonic plague (Black Death) led to increased efforts in public health, including improved sanitation practices and the establishment of quarantine measures for infected individuals.

6. Humoral theory: Although challenged by some during this period, the ancient Greek humoral theory—which posited that the balance of four bodily fluids or "humors" (blood, phlegm, black bile, and yellow bile) determined a person's health—remained influential in medical practice.

7. Surgery: Barber-surgeons continued to perform various surgical procedures, including bloodletting, tooth extraction, and amputations. However, anesthesia was still not widely used, and pain management relied on opium or alcohol-based preparations.

8. Pharmacology: The use of herbal remedies and other natural substances to treat illnesses remained popular during the 15th century. Physicians like Nicholas Culpeper (1616–1654) compiled extensive lists of medicinal plants and their uses, contributing to the development of modern pharmacology.

9. Astrology and medicine: Despite growing skepticism among some scholars, astrological beliefs continued to influence medical practice in the 15th century. Physicians often consulted astrological charts when diagnosing and treating patients.

10. Medical education: Universities across Europe offered formal medical education, with students studying anatomy, physiology, pathology, and pharmacology. However, many practitioners still learned their trade through apprenticeships or self-study.

CD4-positive T-lymphocytes, also known as CD4+ T cells or helper T cells, are a type of white blood cell that plays a crucial role in the immune response. They express the CD4 receptor on their surface and help coordinate the immune system's response to infectious agents such as viruses and bacteria.

CD4+ T cells recognize and bind to specific antigens presented by antigen-presenting cells, such as dendritic cells or macrophages. Once activated, they can differentiate into various subsets of effector cells, including Th1, Th2, Th17, and Treg cells, each with distinct functions in the immune response.

CD4+ T cells are particularly important in the immune response to HIV (human immunodeficiency virus), which targets and destroys these cells, leading to a weakened immune system and increased susceptibility to opportunistic infections. The number of CD4+ T cells is often used as a marker of disease progression in HIV infection, with lower counts indicating more advanced disease.

I believe there might be a bit of confusion in your question. A "history" in medical terms usually refers to the detailed account of a patient's symptoms, illnesses, and treatments over time. It is a crucial part of the medical record and helps healthcare professionals understand the patient's health status and inform their care plans.

On the other hand, "16th century" refers to a specific period in history, spanning from 1501 to 1600 AD.

There isn't a direct medical definition for 'History, 16th Century.' However, if you are interested in learning about the medical advancements and practices during that time, I would be happy to provide some information. The 16th century was marked by significant developments in anatomy, surgery, and pharmacology, thanks to pioneers like Andreas Vesalius, Ambroise Paré, and William Shakespeare, who incorporated medical themes into his plays.

GATA3 transcription factor is a protein that plays a crucial role in the development and function of various types of cells, particularly in the immune system and the nervous system. It belongs to the family of GATA transcription factors, which are characterized by their ability to bind to specific DNA sequences through a zinc finger domain.

The GATA3 protein is encoded by the GATA3 gene, which is located on chromosome 10 in humans. This protein contains two zinc fingers that allow it to recognize and bind to the GATAA sequence in the DNA. Once bound, GATA3 can regulate the transcription of nearby genes, either activating or repressing their expression.

In the immune system, GATA3 is essential for the development of T cells, a type of white blood cell that plays a central role in the adaptive immune response. Specifically, GATA3 helps to promote the differentiation of naive T cells into Th2 cells, which produce cytokines that are involved in the defense against parasites and allergens.

In addition to its role in the immune system, GATA3 has also been implicated in the development and function of the nervous system. For example, it has been shown to play a role in the differentiation of neural crest cells, which give rise to various types of cells in the peripheral nervous system.

Mutations in the GATA3 gene have been associated with several human diseases, including HDR syndrome (hypoparathyroidism, deafness, and renal dysplasia) and certain types of cancer, such as breast cancer and bladder cancer.

Lymphocyte activation is the process by which B-cells and T-cells (types of lymphocytes) become activated to perform effector functions in an immune response. This process involves the recognition of specific antigens presented on the surface of antigen-presenting cells, such as dendritic cells or macrophages.

The activation of B-cells leads to their differentiation into plasma cells that produce antibodies, while the activation of T-cells results in the production of cytotoxic T-cells (CD8+ T-cells) that can directly kill infected cells or helper T-cells (CD4+ T-cells) that assist other immune cells.

Lymphocyte activation involves a series of intracellular signaling events, including the binding of co-stimulatory molecules and the release of cytokines, which ultimately result in the expression of genes involved in cell proliferation, differentiation, and effector functions. The activation process is tightly regulated to prevent excessive or inappropriate immune responses that can lead to autoimmunity or chronic inflammation.

Interleukin-12 (IL-12) is a naturally occurring protein that is primarily produced by activated macrophages and dendritic cells, which are types of immune cells. It plays a crucial role in the regulation of the immune response, particularly in the development of cell-mediated immunity.

IL-12 is composed of two subunits, p35 and p40, which combine to form a heterodimer. This cytokine stimulates the differentiation and activation of naive T cells into Th1 cells, which are important for fighting intracellular pathogens such as viruses and bacteria. IL-12 also enhances the cytotoxic activity of natural killer (NK) cells and CD8+ T cells, which can directly kill infected or malignant cells.

In addition to its role in the immune response, IL-12 has been implicated in the pathogenesis of several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and psoriasis. As a result, therapeutic strategies targeting IL-12 or its signaling pathways have been explored as potential treatments for these conditions.

Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

T-lymphocyte subsets refer to distinct populations of T-cells, which are a type of white blood cell that plays a central role in cell-mediated immunity. The two main types of T-lymphocytes are CD4+ and CD8+ cells, which are defined by the presence or absence of specific proteins called cluster differentiation (CD) molecules on their surface.

CD4+ T-cells, also known as helper T-cells, play a crucial role in activating other immune cells, such as B-lymphocytes and macrophages, to mount an immune response against pathogens. They also produce cytokines that help regulate the immune response.

CD8+ T-cells, also known as cytotoxic T-cells, directly kill infected cells or tumor cells by releasing toxic substances such as perforins and granzymes.

The balance between these two subsets of T-cells is critical for maintaining immune homeostasis and mounting effective immune responses against pathogens while avoiding excessive inflammation and autoimmunity. Therefore, the measurement of T-lymphocyte subsets is essential in diagnosing and monitoring various immunological disorders, including HIV infection, cancer, and autoimmune diseases.

Ovalbumin is the major protein found in egg white, making up about 54-60% of its total protein content. It is a glycoprotein with a molecular weight of around 45 kDa and has both hydrophilic and hydrophobic regions. Ovalbumin is a single polypeptide chain consisting of 385 amino acids, including four disulfide bridges that contribute to its structure.

Ovalbumin is often used in research as a model antigen for studying immune responses and allergies. In its native form, ovalbumin is not allergenic; however, when it is denatured or degraded into smaller peptides through cooking or digestion, it can become an allergen for some individuals.

In addition to being a food allergen, ovalbumin has been used in various medical and research applications, such as vaccine development, immunological studies, and protein structure-function analysis.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Tyrosine 3-Monooxygenase (also known as Tyrosinase or Tyrosine hydroxylase) is an enzyme that plays a crucial role in the synthesis of catecholamines, which are neurotransmitters and hormones in the body. This enzyme catalyzes the conversion of the amino acid L-tyrosine to 3,4-dihydroxyphenylalanine (L-DOPA) by adding a hydroxyl group to the 3rd carbon atom of the tyrosine molecule.

The reaction is as follows:

L-Tyrosine + O2 + pterin (co-factor) -> L-DOPA + pterin (oxidized) + H2O

This enzyme requires molecular oxygen and a co-factor such as tetrahydrobiopterin to carry out the reaction. Tyrosine 3-Monooxygenase is found in various tissues, including the brain and adrenal glands, where it helps regulate the production of catecholamines like dopamine, norepinephrine, and epinephrine. Dysregulation of this enzyme has been implicated in several neurological disorders, such as Parkinson's disease.

Interleukins (ILs) are a group of naturally occurring proteins that are important in the immune system. They are produced by various cells, including immune cells like lymphocytes and macrophages, and they help regulate the immune response by facilitating communication between different types of cells. Interleukins can have both pro-inflammatory and anti-inflammatory effects, depending on the specific interleukin and the context in which it is produced. They play a role in various biological processes, including the development of immune responses, inflammation, and hematopoiesis (the formation of blood cells).

There are many different interleukins that have been identified, and they are numbered according to the order in which they were discovered. For example, IL-1, IL-2, IL-3, etc. Each interleukin has a specific set of functions and targets certain types of cells. Dysregulation of interleukins has been implicated in various diseases, including autoimmune disorders, infections, and cancer.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays a crucial role in the modulation of immune responses. It is produced by various cell types, including T cells, macrophages, and dendritic cells. IL-10 inhibits the production of pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6, IL-8, and IL-12, and downregulates the expression of costimulatory molecules on antigen-presenting cells. This results in the suppression of T cell activation and effector functions, which ultimately helps to limit tissue damage during inflammation and promote tissue repair. Dysregulation of IL-10 has been implicated in various pathological conditions, including chronic infections, autoimmune diseases, and cancer.

Nuclear Receptor Subfamily 1, Group F, Member 3 (NR1F3) is a gene that encodes for the retinoic acid-related orphan receptor alpha (RORα) protein. RORα is a type of nuclear receptor, which are transcription factors that regulate gene expression in response to various signals, including hormones and other molecules. RORα plays important roles in several biological processes, such as the regulation of circadian rhythm, immune function, and metabolism.

NR1F3/RORα has been identified as a critical regulator of the development and function of various immune cells, including T cells, B cells, and dendritic cells. It is also involved in the regulation of lipid metabolism and energy homeostasis, and its dysregulation has been implicated in several metabolic disorders, such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease.

Furthermore, NR1F3/RORα has been shown to play a role in the development of certain cancers, including breast cancer, prostate cancer, and leukemia. Therefore, understanding the function and regulation of NR1F3/RORα is an active area of research with potential therapeutic implications for various diseases.

Dendritic cells (DCs) are a type of immune cell that play a critical role in the body's defense against infection and cancer. They are named for their dendrite-like projections, which they use to interact with and sample their environment. DCs are responsible for processing antigens (foreign substances that trigger an immune response) and presenting them to T cells, a type of white blood cell that plays a central role in the immune system's response to infection and cancer.

DCs can be found throughout the body, including in the skin, mucous membranes, and lymphoid organs. They are able to recognize and respond to a wide variety of antigens, including those from bacteria, viruses, fungi, and parasites. Once they have processed an antigen, DCs migrate to the lymph nodes, where they present the antigen to T cells. This interaction activates the T cells, which then go on to mount a targeted immune response against the invading pathogen or cancerous cells.

DCs are a diverse group of cells that can be divided into several subsets based on their surface markers and function. Some DCs, such as Langerhans cells and dermal DCs, are found in the skin and mucous membranes, where they serve as sentinels for invading pathogens. Other DCs, such as plasmacytoid DCs and conventional DCs, are found in the lymphoid organs, where they play a role in activating T cells and initiating an immune response.

Overall, dendritic cells are essential for the proper functioning of the immune system, and dysregulation of these cells has been implicated in a variety of diseases, including autoimmune disorders and cancer.

Transgenic mice are genetically modified rodents that have incorporated foreign DNA (exogenous DNA) into their own genome. This is typically done through the use of recombinant DNA technology, where a specific gene or genetic sequence of interest is isolated and then introduced into the mouse embryo. The resulting transgenic mice can then express the protein encoded by the foreign gene, allowing researchers to study its function in a living organism.

The process of creating transgenic mice usually involves microinjecting the exogenous DNA into the pronucleus of a fertilized egg, which is then implanted into a surrogate mother. The offspring that result from this procedure are screened for the presence of the foreign DNA, and those that carry the desired genetic modification are used to establish a transgenic mouse line.

Transgenic mice have been widely used in biomedical research to model human diseases, study gene function, and test new therapies. They provide a valuable tool for understanding complex biological processes and developing new treatments for a variety of medical conditions.

Interleukin-13 (IL-13) is a cytokine that plays a crucial role in the immune response, particularly in the development of allergic inflammation and hypersensitivity reactions. It is primarily produced by activated Th2 cells, mast cells, basophils, and eosinophils. IL-13 mediates its effects through binding to the IL-13 receptor complex, which consists of the IL-13Rα1 and IL-4Rα chains.

IL-13 has several functions in the body, including:

* Regulation of IgE production by B cells
* Induction of eosinophil differentiation and activation
* Inhibition of proinflammatory cytokine production by macrophages
* Promotion of mucus production and airway hyperresponsiveness in the lungs, contributing to the pathogenesis of asthma.

Dysregulation of IL-13 has been implicated in various diseases, such as allergic asthma, atopic dermatitis, and chronic rhinosinusitis. Therefore, targeting IL-13 with biologic therapies has emerged as a promising approach for the treatment of these conditions.

Interleukin-5 (IL-5) is a type of cytokine, which is a small signaling protein that mediates and regulates immunity, inflammation, and hematopoiesis. IL-5 is primarily produced by activated T cells, especially Th2 cells, as well as mast cells, eosinophils, and innate lymphoid cells (ILCs).

The primary function of IL-5 is to regulate the growth, differentiation, activation, and survival of eosinophils, a type of white blood cell that plays a crucial role in the immune response against parasitic infections. IL-5 also enhances the ability of eosinophils to migrate from the bone marrow into the bloodstream and then into tissues, where they can participate in immune responses.

In addition to its effects on eosinophils, IL-5 has been shown to have a role in the regulation of B cell function, including promoting the survival and differentiation of B cells into antibody-secreting plasma cells. Dysregulation of IL-5 production and activity has been implicated in several diseases, including asthma, allergies, and certain parasitic infections.

Regulatory T-lymphocytes (Tregs), also known as suppressor T cells, are a subpopulation of T-cells that play a critical role in maintaining immune tolerance and preventing autoimmune diseases. They function to suppress the activation and proliferation of other immune cells, thereby regulating the immune response and preventing it from attacking the body's own tissues.

Tregs constitutively express the surface markers CD4 and CD25, as well as the transcription factor Foxp3, which is essential for their development and function. They can be further divided into subsets based on their expression of other markers, such as CD127 and CD45RA.

Tregs are critical for maintaining self-tolerance by suppressing the activation of self-reactive T cells that have escaped negative selection in the thymus. They also play a role in regulating immune responses to foreign antigens, such as those encountered during infection or cancer, and can contribute to the immunosuppressive microenvironment found in tumors.

Dysregulation of Tregs has been implicated in various autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and multiple sclerosis, as well as in cancer and infectious diseases. Therefore, understanding the mechanisms that regulate Treg function is an important area of research with potential therapeutic implications.

Interleukin-23 (IL-23) is a pro-inflammatory cytokine, which is a type of signaling molecule used for communication between cells in the immune system. It is a heterodimeric protein composed of two subunits: p19 and p40. IL-23 plays a crucial role in the adaptive immune response by promoting the differentiation and activation of T-cells, particularly Th17 cells, which are involved in inflammatory responses.

IL-23 is produced primarily by activated dendritic cells and macrophages in response to various stimuli such as pathogens or tissue damage. Dysregulation of IL-23 has been implicated in several autoimmune diseases, including psoriasis, inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. Therefore, therapeutic strategies targeting IL-23 are being explored as potential treatments for these conditions.

T-box domain proteins are a family of transcription factors that share a highly conserved DNA-binding domain, known as the T-box. The T-box domain is a DNA-binding motif that specifically recognizes and binds to T-box binding elements (TBEs) in the regulatory regions of target genes. These proteins play crucial roles during embryonic development, particularly in the formation of specific tissues and organs, such as the heart, limbs, and brain. Mutations in T-box domain proteins can lead to various congenital defects and developmental disorders. Some examples of T-box domain proteins include TBX1, TBX5, and TBX20.

Immunologic adjuvants are substances that are added to a vaccine to enhance the body's immune response to the antigens contained in the vaccine. They work by stimulating the immune system and promoting the production of antibodies and activating immune cells, such as T-cells and macrophages, which help to provide a stronger and more sustained immune response to the vaccine.

Immunologic adjuvants can be derived from various sources, including bacteria, viruses, and chemicals. Some common examples include aluminum salts (alum), oil-in-water emulsions (such as MF59), and bacterial components (such as lipopolysaccharide or LPS).

The use of immunologic adjuvants in vaccines can help to improve the efficacy of the vaccine, particularly for vaccines that contain weak or poorly immunogenic antigens. They can also help to reduce the amount of antigen needed in a vaccine, which can be beneficial for vaccines that are difficult or expensive to produce.

It's important to note that while adjuvants can enhance the immune response to a vaccine, they can also increase the risk of adverse reactions, such as inflammation and pain at the injection site. Therefore, the use of immunologic adjuvants must be carefully balanced against their potential benefits and risks.

The spleen is an organ in the upper left side of the abdomen, next to the stomach and behind the ribs. It plays multiple supporting roles in the body:

1. It fights infection by acting as a filter for the blood. Old red blood cells are recycled in the spleen, and platelets and white blood cells are stored there.
2. The spleen also helps to control the amount of blood in the body by removing excess red blood cells and storing platelets.
3. It has an important role in immune function, producing antibodies and removing microorganisms and damaged red blood cells from the bloodstream.

The spleen can be removed without causing any significant problems, as other organs take over its functions. This is known as a splenectomy and may be necessary if the spleen is damaged or diseased.

STAT6 (Signal Transducer and Activator of Transcription 6) is a transcription factor that plays a crucial role in the immune response, particularly in the development of Th2 cells and the production of cytokines. It is activated by cytokines such as IL-4 and IL-13 through phosphorylation, which leads to its dimerization and translocation into the nucleus where it binds to specific DNA sequences and regulates the expression of target genes. STAT6 is involved in a variety of biological processes including allergic responses, inflammation, and tumorigenesis. Mutations in the STAT6 gene have been associated with immunodeficiency disorders and certain types of cancer.

Flow cytometry is a medical and research technique used to measure physical and chemical characteristics of cells or particles, one cell at a time, as they flow in a fluid stream through a beam of light. The properties measured include:

* Cell size (light scatter)
* Cell internal complexity (granularity, also light scatter)
* Presence or absence of specific proteins or other molecules on the cell surface or inside the cell (using fluorescent antibodies or other fluorescent probes)

The technique is widely used in cell counting, cell sorting, protein engineering, biomarker discovery and monitoring disease progression, particularly in hematology, immunology, and cancer research.

Adoptive transfer is a medical procedure in which immune cells are transferred from a donor to a recipient with the aim of providing immunity or treating a disease, such as cancer. This technique is often used in the field of immunotherapy and involves isolating specific immune cells (like T-cells) from the donor, expanding their numbers in the laboratory, and then infusing them into the patient. The transferred cells are expected to recognize and attack the target cells, such as malignant or infected cells, leading to a therapeutic effect. This process requires careful matching of donor and recipient to minimize the risk of rejection and graft-versus-host disease.

Immunoglobulin E (IgE) is a type of antibody that plays a key role in the immune response to parasitic infections and allergies. It is produced by B cells in response to stimulation by antigens, such as pollen, pet dander, or certain foods. Once produced, IgE binds to receptors on the surface of mast cells and basophils, which are immune cells found in tissues and blood respectively. When an individual with IgE antibodies encounters the allergen again, the cross-linking of IgE molecules bound to the FcεRI receptor triggers the release of mediators such as histamine, leukotrienes, prostaglandins, and various cytokines from these cells. These mediators cause the symptoms of an allergic reaction, such as itching, swelling, and redness. IgE also plays a role in protecting against certain parasitic infections by activating eosinophils, which can kill the parasites.

In summary, Immunoglobulin E (IgE) is a type of antibody that plays a crucial role in the immune response to allergens and parasitic infections, it binds to receptors on the surface of mast cells and basophils, when an individual with IgE antibodies encounters the allergen again, it triggers the release of mediators from these cells causing the symptoms of an allergic reaction.

Animal disease models are specialized animals, typically rodents such as mice or rats, that have been genetically engineered or exposed to certain conditions to develop symptoms and physiological changes similar to those seen in human diseases. These models are used in medical research to study the pathophysiology of diseases, identify potential therapeutic targets, test drug efficacy and safety, and understand disease mechanisms.

The genetic modifications can include knockout or knock-in mutations, transgenic expression of specific genes, or RNA interference techniques. The animals may also be exposed to environmental factors such as chemicals, radiation, or infectious agents to induce the disease state.

Examples of animal disease models include:

1. Mouse models of cancer: Genetically engineered mice that develop various types of tumors, allowing researchers to study cancer initiation, progression, and metastasis.
2. Alzheimer's disease models: Transgenic mice expressing mutant human genes associated with Alzheimer's disease, which exhibit amyloid plaque formation and cognitive decline.
3. Diabetes models: Obese and diabetic mouse strains like the NOD (non-obese diabetic) or db/db mice, used to study the development of type 1 and type 2 diabetes, respectively.
4. Cardiovascular disease models: Atherosclerosis-prone mice, such as ApoE-deficient or LDLR-deficient mice, that develop plaque buildup in their arteries when fed a high-fat diet.
5. Inflammatory bowel disease models: Mice with genetic mutations affecting intestinal barrier function and immune response, such as IL-10 knockout or SAMP1/YitFc mice, which develop colitis.

Animal disease models are essential tools in preclinical research, but it is important to recognize their limitations. Differences between species can affect the translatability of results from animal studies to human patients. Therefore, researchers must carefully consider the choice of model and interpret findings cautiously when applying them to human diseases.

STAT4 (Signal Transducer and Activator of Transcription 4) is a transcription factor protein that plays a crucial role in the immune response. When activated, STAT4 translocates to the nucleus and binds to specific DNA sequences, regulating the expression of target genes involved in various cellular processes such as differentiation, proliferation, and activation of immune cells like T-cells.

Activation of STAT4 occurs through phosphorylation by receptor associated kinases, following cytokine stimulation, particularly interleukin (IL)-12 and type I interferons. Once activated, STAT4 forms homodimers or heterodimers with other STAT proteins, which then translocate to the nucleus and bind to specific DNA sequences called gamma-activated sites (GAS) in the promoter regions of target genes.

Mutations in the STAT4 gene have been associated with various autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, highlighting its importance in maintaining immune homeostasis.

Autoimmune encephalomyelitis (EAE) is a model of inflammatory demyelinating disease used in medical research to study the mechanisms of multiple sclerosis (MS) and develop new therapies. It is experimentally induced in laboratory animals, typically mice or rats, through immunization with myelin antigens or T-cell transfer. The resulting immune response leads to inflammation, demyelination, and neurological dysfunction in the central nervous system (CNS), mimicking certain aspects of MS.

EAE is a valuable tool for understanding the pathogenesis of MS and testing potential treatments. However, it is essential to recognize that EAE is an experimental model and may not fully recapitulate all features of human autoimmune encephalomyelitis.

An allergen is a substance that can cause an allergic reaction in some people. These substances are typically harmless to most people, but for those with allergies, the immune system mistakenly identifies them as threats and overreacts, leading to the release of histamines and other chemicals that cause symptoms such as itching, sneezing, runny nose, rashes, hives, and difficulty breathing. Common allergens include pollen, dust mites, mold spores, pet dander, insect venom, and certain foods or medications. When a person comes into contact with an allergen, they may experience symptoms that range from mild to severe, depending on the individual's sensitivity to the substance and the amount of exposure.

Romagnani S (November 1999). "Th1/Th2 cells". Inflammatory Bowel Diseases. 5 (4): 285-94. doi:10.1002/ibd.3780050410. PMID ... Integrins mediate adhesion, signaling, and migration in many different types of cells. During active periods of disease, cell ... Also, the cell-based manufacturing process of biologics results in undefinable post-translational modifications. Thus, it is ... IL-12 and IL-23 help with the activation and differentiation of natural killer cells and CD4+ T lymphocyte, both of which ...
Th3 cells can also directly suppress Th1 and Th2 cells by secretion of TGF-β and provide help to B cells towards IgA secretion ... Th3 inhibits Th1 and Th2 cells. Th3 cells have different cytokine requirements for their growth from CD25+CD4+ Treg cells. The ... Th3 cells are characterised as CD4+CD25−CD69+FOXP3-LAP+ cells. Unlike the well characterised T regulatory (Treg ) cells, Th3 ... LAG3 acts as a negative regulator of T cell activation and function and can also be expressed on NK cells and other T cells, ...
Zhang Y, Zhang Y, Gu W, Sun B (2014). "Th1/Th2 Cell Differentiation and Molecular Signals". T Helper Cell Differentiation and ... which promotes TH2 differentiation. Gata3 enhances T helper cell 2 (Th2) differentiation signals by regulating BHLHE41 ... in sarcoma cells and oral cancer cells. BHLHE41 also suppresses cytochrome P450 2D6 (CYP2D6) in hepatocellular carcinoma cells ... and metastasis in sarcoma cells and hepatocellular carcinoma cells. It has been shown that the normal tissue adjacent to colon ...
Lesterhuis WJ, Steer H, Lake RA (October 2011). "PD-L2 is predominantly expressed by Th2 cells". Molecular Immunology. 49 (1-2 ... In mouse cell cultures, PD-L2 expression on tumor cells suppressed cytotoxic T cell-mediated immune responses. Indirectly, PD- ... PD-L2 is one of two known ligands for Programmed cell death protein 1 (PD-1). PD-L2 is a cell surface receptor belonging to the ... Others have shown PD-L2 expression in certain T helper cell subsets and cytotoxic T cells. PD-L2 protein is widely expressed in ...
Th cells), particularly Th2 cells. Group 2 ILCs and Th2 cells, and thereby GATA3, are critical for the development of allergic ... "The Transcription Factor GATA-3 Is Necessary and Sufficient for Th2 Cytokine Gene Expression in CD4 T Cells". Cell. 89 (4): 587 ... The Transcription Factor GATA-3 Is Necessary and Sufficient for Th2 Cytokine Gene Expression in CD4 T Cells. Cell. 1997. 89: ... is critical for the embryonic development and/or function of various cell types (e.g. fat cells, neural crest cells, ...
... expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells". Proceedings of the ... In humans, cell surface expression of ICOSLG has been described on B cells, dendritic cells, monocytes/macrophages, and T cells ... expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells". Proceedings of the ... it diminished B cell costimulation of T cells. It led to defect in antibody and memory B cell generation. Mutant ICOSLG also ...
Th2 cells are the other Th cell polarization initially defined. Th2 differentiation is dependent on the presence of IL-4 and ... CD4+ T cells (mature T-helper cells) play an important role in modulating immune responses to pathogens and tumor cells, and ... complicating the role of Th2 cells in tumor immunity. Th17 are a recently identified subset of Th cells that are primarily ... and signature cytokines of Th2 cells include IL-4, IL-5, and IL-13. Th2 mediated anti-tumor activity primarily involves ...
... an increase in the expression of DP2 by these cells, an enhanced rate of differentiation of precursor cells to Th2 cells in ... see T helper cell#Th1/Th2 Model for helper T cells) by binding to a receptor initially termed GPR44 and thereafter CRTH2 (for ... and Th2 cells at sites of nascent inflammation in animal models. PGD2, acting through DP2, stimulates the in vitro chemotaxis ... and Th2 cells. DP2 activation also stimulates eosinophils and basophils to release the many pro-allergic elements of their ...
It is thought to be important for Th2 cells in particular. The protein encoded by this gene belongs to the CD28 and CTLA-4 cell ... It forms homodimers and plays an important role in cell-cell signaling, immune responses and regulation of cell proliferation. ... Compared to wild-type naïve T cells, ICOS-/- T cells activated with plate-bound anti-CD3 have reduced proliferation and IL-2 ... In terms of Th1 and Th2 cytokine secretion, ICOS-/- CD4+ T cell activated in vitro reduced IL-4 secretion, while maintaining ...
while TGF-β alone can switch TH2 cells into TH9 cells. IL-2 is critical for interleukin-9 production by TH9 cells. IL-1 may ... In cell biology, TH9 cells (T helper type 9 cells, CD4+IL-9+IL-13−IFNγ − ) are a sub-population of CD4+T cells that produce ... Th9 cells can differentiate either from naive T lymphocytes or by a shift from TH2 cells. There are numbers of cytokines, ... TH9 cells contribute to ulcerative colitis, due to the cell's ability to impair cellular repair, as well as due to the ability ...
The main effector cells are eosinophils, basophils, and mast cells as well as B cells, and IL-4/IL-5 CD4 T cells. The key Th2 ... Their main effector cells are NK cells as well as CD8 T cells, IgG B cells, and IL-10 CD4 T cells. The key THαβ transcription ... The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role ... IFN-γ drives Th1 cell production while IL-10 and IL-4 inhibit Th1 cell production. Conversely, IL-4 drives Th2 cell production ...
ROG then downregulates GATA-3, a characteristic transcription factor for Th2 cells. Tr1 cells express high levels of regulatory ... cells are a class of regulatory T cells participating in peripheral immunity as a subsets of CD4+ T cells. Tr1 cells regulate ... The suppressing and tolerance-inducing effect of Tr1 cells is mediated mainly by cytokines. The other mechanism as cell to cell ... LAG-3 activates dendritic cells (DCs) and enhances the antigen-specific T-cell response which is necessary for Tr1 cells ...
36 with McCusker noting in her expert report that the only marker of Th2 cell activity that was assessed in Michelle's case, ... Brent argued that the Goth study was flawed because it tested thimerosal on mouse cells, not human cells; because these cells ... "Thimerosal induces TH2 responses via influencing cytokine secretion by human dendritic cells". Journal of Leukocyte Biology. 81 ... Brent highlighted similar problems with the Agrawal study, noting that the cells in that study, like those in the Goth study, ...
Boyton, Rosemary Jane (2000). T cell receptor signalling in TH1 and TH2 cytokine responses in autoimmunity. (PhD ... In allergic asthma, lung inflammation is caused by a CD4 T cell that attacks otherwise harmless allergens. This attack can ... "Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease". Clinical & ... research fellowship to complete a PhD at Imperial College London where she studied the mechanisms that underpin T helper cell ...
Activation of Th2 cells is an important part of this feed-forward loop. The activation of tuft cells in the intestine is ... Tuft cells are chemosensory cells in the epithelial lining of the intestines. Similar tufted cells are found in the respiratory ... Also during worm infection, the amount of tuft cells dramatically rises. Hyperplasia of tuft cells and goblet cells is a ... These cells were located between the crypts and villi. On the basal pole of all cells was expressed DCLK1. They did not have ...
TH2). Basophils are one of the least abundant cells in bone marrow and blood (occurring at less than two percent of all cells ... they regulate other immune cell functions (e.g., CD4+ T cell, dendritic cell, B cell, mast cell, neutrophil, and basophil ... These cells also have a limited ability to participate in phagocytosis, they are professional antigen-presenting cells, ... Granulocytes are derived from stem cells residing in the bone marrow. The differentiation of these stem cells from multipotent ...
"Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene". Immunity. 15 (2): 275-87. doi:10.1016/S1074 ... The expression of this gene was detected in various tumor cells, but is limited in neural organs in normal tissues. Knockout ... Guo WJ, Datta S, Band V, Dimri GP (February 2007). "Mel-18, a polycomb group protein, regulates cell proliferation and ... October 2016). "A High-Density Map for Navigating the Human Polycomb Complexome". Cell Reports. 17 (2): 583-595. doi:10.1016/j. ...
... specially Th2-differentiated T cells and a subset of T regulatory cells in vitro into inflammatory siter. It can also attract ... July 1998). "The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells". Journal of Immunology. 161 (2 ... For example, CCL1 transcription was increased in primary human CD4+ T cells expressing T cell immunoglobulin and protein 3 ... CCl1 has also been studied as a possible potent inhibitor of fusion of cells and cells mediated by HIV-1 envelope and viral ...
"Soluble CD83 alleviates experimental allergic rhinitis through modulating antigen-specific Th2 cell property". International ... T regulatory cells (Treg cells) are present in two major populations: thymically induced and peripherally induced Treg cells. ... "A novel cell-surface molecule expressed by human interdigitating reticulum cells, Langerhans cells, and activated lymphocytes ... "Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83". ...
"Enhanced CD4+ T cell proliferation and Th2 cytokine production in DR6-deficient mice". Immunity. 15 (1): 23-34. doi:10.1016/ ... Tumor cells can induce, through exposition of amyloid precursor protein (APP), DR6-mediated endothelial cell necroptosis ... It is mostly expressed in the thymus, spleen and white blood cells. The Gene for DR6 is 78,450 bases long and is found on the ... Knockout studies in mice suggested that this gene plays a role in T helper cell activation, and may be involved in inflammation ...
Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles. Journal of Experimental Medicine 214 ( ... An infection model of N. brasiliensis has been used to determine that at least two distinct Th2-type immune responses occur - ... Among respiratory problems, a N. brasiliensis infection can also result in the loss of both body mass and red blood cell ... For instance, they can provide the model for induction and maintenance of Th2 type immune responses and exhibit all the ...
In cattle Th1 and Th2 cells are an important part of the response. Neither cell type expresses exclusively IFNγ or IL-4 for L. ... Activation of complements occurs far from the cell membrane, and insertion of the membrane attack complex does not occur. This ... As more and more phagocytic cells engulf promastigotes, prompting the production of amastigotes, nodules form on the skin. ... King, DL; Chang Y-D; Turco SJ (1987). "Cell surface lipophosphoglycan of Leishmania donovani". Molecular and Biochemical ...
May 2009). "T follicular helper cells differentiate from Th2 cells in response to helminth antigens". J Exp Med. 206 (5): 991-9 ... Pre-TFH cells are functionally very similar to other TFH cells in facilitating germinal center B cell reactions; however, they ... This may be in part due to lower CD40L levels on the cell surface of TFH cells in the aged. Unchecked or overactive TFH cell ... TFH cell-dependent paracrine activation of B cell CD40 results in B cell survival and differentiation, including the induction ...
Saenz, SA; Noti, M; Artis, D (Nov 2010). "Innate immune cell populations function as initiators and effectors in Th2 cytokine ... These include Natural Helper Cells (NHCs), Innate Helper 2 (Ih2) cells and multi-potent progenitor (MPP) type 2 cells. The ... Innate lymphoid cell (Lymphocytes, Cells, Human cells, Immunology, Immune system). ... Pro-T cell progenitors retain nuocyte developmental potential but, unlike T cells, the thymus is dispensable for their ...
"The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells". J. Immunol. 161 (2): 547-51. PMID 9670926. ... "Identification of the chemokine receptor TER1/CCR8 expressed in brain-derived cells and T cells as a new coreceptor for HIV-1 ... "Characterization of chemokine receptors expressed in primitive blood cells during human hematopoietic ontogeny". Stem Cells. 18 ... Studies of this receptor and its ligands suggested its role in regulation of monocyte chemotaxis and thymic cell apoptosis. ...
Th2) Unlike other lymphoid lineages, T cell development occurs almost exclusively in the thymus. T-lymphopoiesis does not occur ... B cells Large Pre-B cells => Small Pre-B cells Immature B cells B Cells => (B1 cells; B2 cells) Plasma cells Pro-T cells T- ... T cells, B cells and NK cells (and all other Innate lymphoid cells) are unique to the lymphocyte family, but dendritic cells ... NK cells Dendritic cells (lymphoid lineage; DC2 ) Progenitor B cells Pro-B cells => Early Pro (or pre-pre)-B cells => Late Pro ...
... cells. Th cells can polarize into Th1 or Th2 effector cells depending on the presence of cytokines. High expression of CLIP ... This occurs in most cells expressing MHC II-however, in B cells, HLA-DO functions as the accessory protein. Both HLA-DM and HLA ... CLIP also can affect the differentiation of T cells. MHC II + CLIP complexes are upregulated on maturing dendritic cells, which ... favors the release of IL-4 and Th2 cell polarization. CLIP plays an important role in preventing autoimmunity. Since MHC is a ...
Allergens elicit a Th2 immune response, including the involvement of IgE, mast cells, Innate lymphoid cells 2 (ILC2), ... B cells also have a decreased repertoire of naïve cells and an increase in memory B cells. They also have reduced the ... In contrast to severe T cell immunodeficiency, some of T-cell ability to respond to infections can be maintained. T-cell ... The production of mucus is promoted by IL-13 from ILC2 and Th2 cells. Higher mucus production then creates stronger barrier ...
Zhu J (September 2015). "T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation ... Retinoic acid, produced by many cell types, such as nerve cells, dendritic cells, and stromal cells, favours the ... T cells stimulate goblet cell mucus secretion, contraction of smooth muscle, and they secrete signals recruiting mast cells and ... NK cells are cytotoxic cells, circulating in the bloodstream, killing virus-infected, and tumor cells. ILC1s, are non- ...
Th9 cells can arise not only from naive T cells but also from differentiated Th2 cells. Another function of IL-25 is the ... These cells include T cells, dendritic cells, macrophages, mast cells, basophils, eosinophils, epithelial cells and Paneth ... Evidence is the expression of IL-17RB on Th2 cells, not on Th1 and Th17. In addition, IL-25 is responsible for the decrease in ... "IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells". The ...
Interactions between ILC2 cells and the adaptive immune system, as well as examination of potential roles for ILC2 cells in the ... These group 2 or type 2 innate lymphoid cells (ILC2 cells) represent a critical source of type 2 cytokines in vivo and serve an ... Further characterization of ILC2 cell biology will enhance the understanding of type 2 responses and may identify new ... The initiation of type 2 immune responses by the epithelial cell-derived cytokines IL-25, IL-33 and TSLP has been an area of ...
The transcription factors SPDEF and FOXA3 are both selectively expressed in epithelial cells lining the condu … ... Epithelial cells that line the conducting airways provide the initial barrier and innate immune responses to the abundant ... Airway epithelial SPDEF integrates goblet cell differentiation and pulmonary Th2 inflammation J Clin Invest. 2015 May;125(5): ... SPDEF was required for goblet cell differentiation and pulmonary Th2 inflammation in response to house dust mite (HDM) extract ...
Surprisingly, Th1 cells did not attenuate Th2 cell-induced airway hyperreactivity and inflammation in either SCID mice or in ... Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation ... Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation ... cells in a mouse model of asthma and examined the capacity of Th1 cells to counterbalance the proasthmatic effects of Th2 cells ...
Conclusions: Our results reveal an association between onset of MCD and activation of Th2 cells. The GRO family has been ... We explored whether GPF was the consequence of Th2 cell activation. Methods: Peripheral blood leukocytes (PBL) from 16 MCD ... Results: Flow cytometry demonstrated a significant expansion of CD4+ T cell population and dramatically increased CD69+ cells ... RT-PCR on RNA from either freshly isolated PBL or post in vitroactivation showed high-level expression of the Th2 cytokine ...
... quizlet biology cells review biology cells study biology cells study guide biology cells test biology cells unit biology cells ... biology cells gap junctions biology cells notes biology cells parts biology cells pdf biology cells practice test biology cells ... types antibodies vs immunity biology cells 10th grade notes biology cells and energy biology cells and molecules biology cells ... unit test biology cells unit test answers biology cells word search biology cells worksheet biology cells worksheets pdf ...
A recent study demonstrated the transdifferentiation of T helper type 2 cell (Th2)-like regulatory T cells (Tregs) in SSc ... Th2- and Th17-like cell proportions in skin-homing Tregs were increased in bleomycin-treated Fli1 +/− mice compared with ... bleomycin-treated wild-type mice, whereas Th1-, Th2-, and Th17-like cell proportions in splenic Tregs were comparable. Fli1+/− ... Under the same coculture condition, an increased tendency of IL-17A-producing cell proportion, which was possibly mediated by ...
... quizlet biology cells review biology cells study biology cells study guide biology cells test biology cells unit biology cells ... biology cells gap junctions biology cells notes biology cells parts biology cells pdf biology cells practice test biology cells ... types antibodies vs immunity biology cells 10th grade notes biology cells and energy biology cells and molecules biology cells ... unit test biology cells unit test answers biology cells word search biology cells worksheet biology cells worksheets pdf ...
SAP controls T cell responses to virus and terminal differentiation of TH2 cells Share Share Share ... SAP controls T cell responses to virus and terminal differentiation of TH2 cells ...
... dendritic cells, and B cells. IL-6 is involved in the acute phase response, B cell maturation, and macrophage differentiation. ... 6 is a cytokine produced by several cell types including antigen presenting cells (APC) such as macrophages, ... T cells and their differentiation into effector Th2 cells. While the induction of Th2 differentiation by IL-6 is dependent upon ... dendritic cells, and B cells. IL-6 is involved in the acute phase response, B cell maturation, and macrophage differentiation. ...
Induction of Th2 cell differentiation in the primary immune response: dendritic cells isolated from adherent cell culture ... Histamine polarizes human dendritic cells into Th2 cell-promoting effector dendritic cells. J. Immunol. ... This results in the polarization of precursor naive Th cells into effector IL-4-producing Th2 cells and is accompanied by ... Promotes Th2 Cell Development and Increased IL-10 Production Through Modulation of Dendritic Cells1 Pedro L. Vieira; Pedro L. ...
The bi-stable switch would enable T cells to integrate signals from pathogens, hormones, cell-cell interactions, and soluble ... The bi-stable switch would enable T cells to integrate signals from pathogens, hormones, cell-cell interactions, and soluble ... CD4+ T-regulatory cell and CD4+ T-regulatory cell type 1 (Tr1) cell functions, and a Th1-Tr1 switch. The proposed Th1-Tr1 ... effector Th1 and Th17 pathogenesis and responsiveness to extrinsic cell death signals, FoxP3+CD4+ Treg cell and CD4+ Tr1 cell ...
Romagnani S (November 1999). "Th1/Th2 cells". Inflammatory Bowel Diseases. 5 (4): 285-94. doi:10.1002/ibd.3780050410. PMID ... Integrins mediate adhesion, signaling, and migration in many different types of cells. During active periods of disease, cell ... Also, the cell-based manufacturing process of biologics results in undefinable post-translational modifications. Thus, it is ... IL-12 and IL-23 help with the activation and differentiation of natural killer cells and CD4+ T lymphocyte, both of which ...
CD4+ T cells are key in mediating the host protective and homeostatic responses. Yet, CD4+ T cells are also known to be the ... Yet, CD4+ T cells are also known to be the main drivers of inflammatory bowel disease (IBD) when this balance is perturbed. ... Many subsets of CD4+ T cells have been identified as players in perpetuating chronic intestinal inflammation. Over the last few ... Many subsets of CD4+ T cells have been identified as players in perpetuating chronic intestinal inflammation. Over the last few ...
Th2 high and mast cell gene signatures are associated with corticosteroid sensitivity in COPD Faiz, A., Pavlidis, S., Kuo, C. H ... Cell-type eQTL deconvolution of bronchial epithelium through integration of single-cell and bulk RNA-seq Qi, C., Berg, M., Chu ... Cell type eQTL deconvolution of bronchial epithelium through integration of single cell and bulk RNA-seq Qi, C., Berg, M., Chu ... An integrated cell atlas of the lung in health and disease Lung Biological Network Consortium, Sikkema, L., Ramírez-Suástegui, ...
... while active Th2 cells secrete IL-4, IL-5, IL-6, IL-10 and IL-136. In addition to Th1 and Th2 cells, Th17, Treg and T Fh cells ... CD4 T cells may assume different phenotypes under different stimulations, changing to Th1 and Th2 cells. They can be ... These findings imply a greater involvement of Th2 cells at this stage of disease, since Th2 cytokines such as IL-4, IL-5, IL-6 ... Usually, protective and destructive roles are assigned to the Th1 and Th173,9-11 cells, while Th2 and Treg cells are more ...
This study was designed to investigate the effects of miR-24 and miR-27 on Th2 in children with non-atopic INS. Methods: ... After that Real-time PCR to investigate the levels of microRNAs and IL-4mRNA, Flow cytometry to test the frequency of Th2 cells ... Results: The proportion of Th2 cells in peripheral blood of children with INS in the initial atopic and non-atopic groups were ... MiR-24 and miR-27 negatively regulate the expression of Th2 cells in children with idiopathic nephrotic syndrome ...
Herein, we generated T cell-specific TRAF4-deficient (CD4-cre Traf4fl/fl) mice and investigated the role of TRAF4 in memory Th2 ... TRAF4 is crucial for ST2+ memory Th2 cell expansion in IL-33-driven airway inflammation. ... TRAF4 is crucial for ST2+ memory Th2 cell expansion in IL-33-driven airway inflammation. ... in ST2+ mTh2 cells stimulated by IL-33. Taken together, the current study reveals a role of TRAF4 in ST2+ mTh2 cells in IL-33- ...
Interestingly, CD8+ T cells and B cells were absent from these rejecting grafts. Even when Th2 cells were introduced directly ... CD4+ T cells and CD11b+ macrophages were present within the graft after adoptive transfer of both Thl and Th2 cells. ... CONCLUSIONS: Th2 and Th0 alloreactive CD4+ T helper cells can reject islet grafts with similar efficiency to Th1 cells. These ... METHODS: Th0, Th1, and Th2 cell lines specific for the class II MHC molecule H2IAb were adoptively transferred into T cell ...
... and Th2 cells without diversion into FoxP3(+) status or substantial effect on Th17 cell differentiation. mTORC2 promoted ... whereas activated PKC-theta reverted only GATA3 transcription factor and the Th2 cell defect of mTORC2 mutant cells. ... connections in T cell differentiation and reveal distinct pathways by which mTORC2 regulates development of Th1 and Th2 cell ... Complementation with active Akt restored only T-bet transcription factor expression and Th1 cell differentiation, ...
... of granuloma formation in IL-1 receptor antagonist-deficient mice with impaired dendritic cell maturation associated with Th2 ... of granuloma formation in IL-1 receptor antagonist-deficient mice with impaired dendritic cell maturation associated with Th2 ...
Cell-Mediated Immunity T-Helper Cells and the Th1-Th2 Shift Systemic Immune Changes Pregnancy and Conventional Infectious ... T-Helper Cells and the Th1-Th2 Shift. Emphasis on cell-mediated immunity versus humoral immunity changes according to the type ... Th2 cells suppress the cytotoxic T lymphocyte response, decreasing the robustness of cell-mediated immunity. In the uterine ... cells. Cells infected with viruses or other intracellular pathogens are cytotoxic T lymphocytes most common targets. The cell- ...
Unbiased and reproducible cataloging of gene expression patterns in distinct cell types requires large numbers of cells. ... While many types of analysis can be carried out and various questions can be answered by single-cell RNA-seq, a central focus ... Measurement of the transcriptomes of single cells has been feasible for only a few years, but it has become an extremely ... Technological developments and protocol improvements have fueled consistent and exponential increases in the number of cells ...
They symbolize another subtype of proinflammatory T-helper cells that differs from Th1 and Th2 cells in development and ... Th2, Th17, and regulatory T cells (Treg) (Physique 1). The first two subsets, Th1 and Th2, were recognized in the 1980s, when ... Development of Th17 cells is usually suppressed by IFNand IL-4 that promote Th1 or Th2 cells, respectively [24]. TGFalone, in ... Unbalanced Th1/Th2 T-cell responses in the liver are a characteristic of. * Post author By globaltechbiz ...
... produced and the degree of Th2 cell chemotaxis were highly correlated. Diclofenac inhibited the production of Th2 cell ... produced by mast cells promotes the migration of Th2 cells through a CRTH2 dependent mechanism. ... The objective was to determine the involvement of prostaglandin D(2) (PGD(2)) and its receptors in the chemotaxis of Th2 cells ... Supernatants from IgE/anti-IgE-stimulated nasal polyp tissue caused significantly increased chemotaxis of Th2 cells. The levels ...
Dive into the research topics of Antigen-pulsed bone marrow-derived and pulmonary dendritic cells promote Th2 cell responses ... Antigen-pulsed bone marrow-derived and pulmonary dendritic cells promote Th2 cell responses and immunopathology in lungs during ...
Increased Plasma Levels of the TH2 chemokine CCL18 associated with low CD4+T cell counts in HIV-1-infected Patients with a ... 2019). Increased Plasma Levels of the TH2 chemokine CCL18 associated with low CD4+T cell counts in HIV-1-infected Patients with ... 2019). Increased Plasma Levels of the TH2 chemokine CCL18 associated with low CD4+T cell counts in HIV-1-infected Patients with ...
BackgroundChemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists are novel agents for asthma ... Th2 Cells, Humans, Asthma, Receptors, Prostaglandin, Receptors, Immunologic, Anti-Asthmatic Agents, Treatment Outcome, ... Efficacy and safety of antagonists for chemoattractant receptor-homologous molecule expressed on Th2 cells in adult patients ... Efficacy and safety of antagonists for chemoattractant receptor-homologous molecule expressed on Th2 cells in adult patients ...
... our data provided evidence that HCG18/hsa-mir-148a-regulated high expression of LAYN is associated with immune cell ... and LAYN expression was found significantly correlated with tumor immune cell infiltration in LIHC tissues. In general, ... cells. Besides, other subpopulations of T cells, such as T helper 1 (Th1), T helper 2 (Th2), follicular helper T (Tfh), Th17, ... CD4+ T cells (. , ), CD8+ T cells (. , ), macrophages (. , ), neutrophils (. , ), and dendritic cells (. , ) in LIHC tissues. ...
Th2 Cells. *Lymphocytes, Tumor-Infiltrating. *Chemokine CXCL9. *Cancer Gene Expression Regulation. *Oligonucleotide Array ... Clear cell renal cell carcinoma (ccRCC) is the most frequent type of renal cell carcinoma (RCC). The present study aimed to ... cell surface receptor signaling pathway - cell-cell signaling - cellular response to heat - chemokine activity - chemotaxis - ... Furthermore, PTTG1 knockdown by shRNA in leukemia cells suppressed cell proliferation, arrested cell-cycle progression and ...
Kim DC, Hsu FI, Barrett NA, et al.: Cysteinyl leukotrienes regulate Th2 cell-dependent pulmonary inflammation. J Immunol 2006, ... dependent mobilization of dendritic cells to lymph nodes. Cell 2000, 103:757-768. ... Okunishi K, Dohi M, Nakagome K, et al.: A novel role of cysteinyl leukotrienes to promote dendritic cell activation in the ... Islam SA, Thomas SY, Hess C, et al.: The leukotriene B4 lipid chemoattractant receptor BLT1 defines antigen-primed T cells in ...
  • Both diseases share clinical and pathological features characteristic of excessive allergen-induced type 2 inflammation, orchestrated by memory CD4(+) T cells that produce type 2 cytokines (Th2 cells). (
  • The mast cells are maintained in the tissue and mucosal surfaces by cytokines such as IL-9 and stem cell factor. (
  • We propose a role for Th17 and Th2 T cells in chronic inflammation in lungs of patients with CF. High concentrations of these cytokines/chemokines in CF airways precede infection with P. aeruginosa. (
  • Objective: We tested the hypotheses that dendritic cells (DCs) respond to IL-33 and that IL-33-activated DCs prime naive CD4 + T cells to produce T H 2-type cytokines. (
  • The ability of IL-33-activated DCs to prime naive T cells was assessed by coculture with isolated CD4 + T cells and by measuring cytokines in the supernatants. (
  • After activation by professional antigen-presenting cells (APCs) such as dendritic cells, macrophages and B cells, antigen-specific CD4+ T cells differentiate into effector cells that are specialized in terms of the cytokines and effector molecules that they express on their membranes or secrete and their discrete effector functions. (
  • The cytokines produced by Th1 cells stimulate the phagocytosis and destruction of microbial pathogens by macrophages and other lymphocytes. (
  • On the other hand, when Th2 cells produce IL-4 and IL-10, these cytokines block the microbial killing that is activated by IFN-γ. (
  • We previously reported on GATA-3+ T-bet+ Th2/1 hybrid cell differentiation in helminth mono-infections, resulting in a substantial proportion of cells co-producing IFN-γ next to Th2 cytokines. (
  • CD4 and CD8 T lymphocytes play an import role in the inflammatory response, as these cells may manage the profile of cytokines produced against an infectious agent 4 . (
  • Progression of periodontal lesions is caused by dysregulation of molecules (cytokines) released by specific cell populations 5 . (
  • They can be distinguished based on the profile of cytokines produced: Th1 cells produce characteristic cytokines such as IL-2, IFN-γ, TNF-β, IL-12, while active Th2 cells secrete IL-4, IL-5, IL-6, IL-10 and IL-136. (
  • POI is associated with an increase in both Th2 cytokines and Th2 cells. (
  • [ 8 ] Airway epithelial cells also release the upstream cytokines in response to noxious agents and recruit T helper-2 and innate lymphoid cells, which secrete IL-5, stimulating the maturation and release of eosinophils ( Figure 1 ). (
  • Upon stimulation, activated Th2 immune cells and type 2 cytokines interact with inflammatory and tissue repair functions to stimulate an overzealous reparative response to tissue damage, leading to organ fibrosis and destruction. (
  • Upon CNT exposure, significant induction and activation of Th2 cells and type 2 cytokines in the lungs are observed. (
  • 2. Analysis of Th1 and Th2 cytokines expressing CD4+ and CD8+ T cells in rheumatoid arthritis by flow cytometry. (
  • 16. Dietary fish oil decreases secretion of T helper (Th) 1-type cytokines by a direct effect on murine splenic T cells but enhances secretion of a Th2-type cytokine by an effect on accessory cells. (
  • Some data suggest that so-called "intrinsic" asthmatics (who have low total IgE levels and no IgE antibodies to known allergens) express the cytokines IL-5 and IFN, that are not characteristic of known T-cell subsets. (
  • The mRNA expression of 25 different types of cytokines in white blood cells was determined by quantitative real time polymerase chain reaction. (
  • Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation. (
  • While IFNγ is a well-known cytokine that actively promotes the type I immune response, it is also known to suppress the type II response by inhibiting the differentiation and proliferation of Th2 cells. (
  • CD23a is expressed by antigen-activated B cells before differentiation into antibody-secreting plasma cells, whereas CD23b expression is induced by IL-4 on a variety of inflammatory cells, B cells and epithelial cells. (
  • The differentiation of mouse naïve CD4 T cells into type 2 helper (Th2) cells is accompanied by chromatin remodeling at the nucleosomes associated with the IL-4, IL-13 and IL-5 genes. (
  • IFN-γ supplementation early during infection supported Th2/1 differentiation, associated with elevated parasite fecundity and the maintenance of high worm burdens in the chronic stage of infection, whereas mice lacking IFN-γ signals generated poor Th2/1 responses and restricted parasite fecundity more efficiently. (
  • Differentiation into Th1 depends on the presence of IFN-γ and IL-12, which bind to receptors on the surface of CD4 T cells 5 . (
  • This binding initiates a cascade of events that culminates in differentiation into Th1 cells, by increasing the transcription factor T-bet 12 . (
  • Th2 cells have a differentiation process which is dependent on IL-4, which causes the activation of the transcription factor STAT 6 . (
  • GATA-3 acts as a master regulator of Th2 differentiation 12-13 . (
  • Thymocyte cell fate is dictated by the nature of TCR-major-histocompatibility-complex (MHC)-peptide interactions, with signals of higher strength leading to death (negative selection) and signals of intermediate strength leading to differentiation (positive selection) 1 . (
  • Our findings uncover a critical regulator of T-cell development that controls the balance between death and differentiation. (
  • The purpose of this review is to summarize and discuss the strategies employed by pathogens to manipulate macrophage differentiation, and in particular their basic cell metabolism, to favor their own growth while avoiding immune control. (
  • Such information is mediated immunity, secreting the cytokine crucial to determine the optimal approach interferon-gamma (IFN) that inhibits Th2 to improve the immune response of DN cell differentiation. (
  • In addition, genes that enhanced Th2 polarization and Th2 cytokine production were also upregulated in asthma. (
  • Leukotriene E4 activates human Th2 cells for exaggerated proinflammatory cytokine production in response to prostaglandin D2. (
  • PGD(2) induced concentration-dependent Th2 cytokine production in the absence of TCR stimulation. (
  • When incubated with naive CD4 + T cells alone, IL-33 failed to stimulate cytokine production. (
  • 1. Beta blocker and angiotensin-converting enzyme inhibitor therapy is associated with decreased Th1/Th2 cytokine ratios and inflammatory cytokine production in patients with chronic heart failure. (
  • 13. Activated T helper 1 and T helper 2 cells differentially express the beta-2-adrenergic receptor: a mechanism for selective modulation of T helper 1 cell cytokine production. (
  • 17. Prostaglandin I2 analogs inhibit Th1 and Th2 effector cytokine production by CD4 T cells. (
  • PGD(2) exerts a number of proinflammatory responses through a high-affinity interaction with chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and has been detected at high concentrations at sites of allergic inflammation. (
  • The DCs' responses to IL-33 were examined by fluorescence-activated cell sorting (MHC-II and CD86 expression) and by ELISA (IL-6 and IL-12 production). (
  • abstract = "Background: IL-33, a recently discovered IL-1 family cytokine, is implicated in the development of TH2-type responses in vivo. (
  • Helper T (Th) cells are essential regulators of adaptive immune responses and inflammatory diseases. (
  • Th2 cells are thought to play a role in allergic responses. (
  • Th1 responses have been implicated in most forms of acute graft or transplant rejection and graft-versus-host (GVHD) disease, while Th2 responses have been variably associated with either protection or chronic rejection. (
  • T helper type 2 (Th2) responses are central to the control of helminth infections, but sensitive to opposing cytokine signals favoring Th1 priming. (
  • These findings suggest that Th2/1 hybrid responses take part in immune regulation during helminth infection and restrain effective anti-helminth immunity. (
  • In this report, we demonstrate that specific inhibition of Lck expression in Th2 cells, in the presence of normal levels of functional Fyn PTK, has profound consequences on multiple events following TCR stimulation, including an altered pattern of tyrosine-phosphorylated substrates, defective phosphorylation of TCR-ζ and ZAP-70, defective Ca 2+ mobilization, and a ∼90% reduction in proliferate responses to antigenic and mitogenic stimuli. (
  • These results demonstrate a dissociation in functional responses in Lck-deficient Th2 cells and suggest a role for Lck in the induction of a state of T cell unresponsiveness. (
  • Our long-term objective is to define how vitamin A regulates T-cell mediated immune responses. (
  • Vitamin A deficiency increases mortality from common childhood infections and impairs immune responses promoted by T-helper type 2 (Th2) cells. (
  • The molecular mechanisms by which vitamin A modulates Th2 responses are not known. (
  • We will then use receptor-selective retinoids and RXR-knockout mice to determine, in vivo, if RXR regulates Th2 cell development and Th2-mediated antibody responses. (
  • Identifying the mechanisms by which vitamin A modulates Th2-mediated immune and inflammatory responses will be useful in several ways. (
  • The Caenorhabditis elegans schnurri homolog sma-9 mediates stage- and cell type-specific responses to DBL-1 BMP-related signaling. (
  • Elucidating key cell signaling pathways and gene and protein expression patterns of the host immune responses in OM pathogenesis using multiple approaches including microarray, RNA-Seq, and mass spectrometry for omics analysis. (
  • Proposed mechanisms to account for the increased susceptibility of individuals with AD to develop KVE or eczema herpeticum (EH) include systemic immune defects involving both cell-mediated and humoral immunity, as well as impairment in cutaneous immune responses that are interrelated with the defective mechanical barrier properties of affected skin in person with AD. (
  • IL-10 induces Th2 responses and regulates T-cell activation. (
  • The experimental vaccine also induced Th1 T-cell responses but not Th2 responses. (
  • Induction of Th2 responses has been associated with a phenomenon called vaccine-associated enhancement of respiratory disease (VAERD). (
  • In addition, the experimental vaccine induced T follicular helper T-cell responses that may have contributed to the robust antibody response. (
  • 3] Recent studies have suggested that IgD-only B cells may play a significant role in immune responses to superantigens. (
  • Thus, efficient Th1 responses are triggered by replicating intracellular pathogens, while Th2 responses would control helminth infection and promote tissue repair during the resolution phase of an infectious event. (
  • Aloe vera gel suppressed Th2 immune responses in mice with food allergy. (
  • 4. Failure of catecholamines to shift T-cell cytokine responses toward a Th2 profile in patients with rheumatoid arthritis. (
  • We hypothesised that a possible indirect mechanism for IL-10 promotion of Th2 cells was via suppression of IFNγ responses as a result of bacteria stimuli. (
  • Furthermore, we found that MLN cells from H. polygyrus infected mice produced IFNγ when stimulated with HES, suggesting that IFNγ responses towards H. polygyrus itself may occur, although the function of this in the immune response to H. polygyrus remains unclear. (
  • In addition, IL-10 optimisation of Th2 responses during helminth infection may be applied to the treatment of helminth infections and other type 2 mediated diseases. (
  • Precise spatial and temporal regulation of cell migration is critical not only for normal immune responses, but also for successful organ development, wound healing, and tumor metastasis. (
  • These results demonstrate that differential clinical responses to OIT are associated with both preexisting characteristics of peanut-reactive CD4+ T cells and suppression of a subset of Th2 cells. (
  • Th2 cells from asthmatic subjects expressed higher levels of several genes that promote their survival as well as alter their metabolic pathways to favor persistence at sites of allergic inflammation. (
  • These cells may be involved in asthma and tissue inflammation. (
  • This study, led by the small business Rapa Therapeutics, LLC and researchers at Massachusetts General Hospital, will investigate RAPA-501, a cell therapy that is designed to reduce inflammation, which may slow disease progression. (
  • Allergen-Experienced Group 2 Innate Lymphoid Cells Acquire Memory-like Properties and Enhance Allergic Lung Inflammation. (
  • Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. (
  • Retinoic-acid-receptor-related orphan nuclear receptor alpha is required for natural helper cell development and allergic inflammation. (
  • TH1, TH2 and TH17 cells instruct monocytes to differentiate into specialized dendritic cell subsets. (
  • This signal together with the T Cell Receptor (TCR) induces the expression of GATA-3. (
  • HIV infection of primary CD4+ Th2 cells, defined by expression of the chemoattractant receptor-homologous (CRTH2), induces a Th0 phenotype. (
  • We have further demonstrated that POI induces a Th2-dependent activation of memory and non-memory B cells. (
  • Knockdown of KDM1B inhibits cell proliferation and induces apoptosis of pancreatic cancer cells. (
  • Aim: To evaluate the involvement of Th2 cells in different periods of the active phase of experimental periodontal disease and expression of the R1 subunit of the receptor for IFN-γ during the early and advanced progression of the disease. (
  • While Th1 immune cells are implicated in POI, the involvement of Th2 cells has not yet been clarified. (
  • However, little is known about how chromatin remodeling of these Th2 cytokine gene loci occurs in human Th2 cells. (
  • Because cysteinyl leukotrienes (cysLTs) are also produced during the allergic response, we investigated the possibility that cysLTs may modulate the response of human Th2 cells to PGD(2). (
  • However, recent publications suggest the existence of a Th2-related cell type that is characterized by the secretion of IL-9 and IL-10. (
  • During an allergic response, the allergen is captured by a preexisting complex of an IgE antibody bound to its high-affinity receptor FcRI on the membrane of mast cells and basophils. (
  • [ 23 , 24 ] This allergen-independent cytokinergic crosslinking of IgE-FcRI complexes involves contact sites in the N-terminal (Fv) domains of IgE for binding to FcRI on the mast cells. (
  • helping eosinophils and monocytes in lysis and phagocytosis of the resulting cell fragments and transport of allergen across the epithelium, and thereafter binding to mast cells and DCs via FcRI. (
  • The enhancing effect was also evident with endogenous cysLTs produced from immunologically activated mast cells because inhibition of cysLT action by montelukast or cysLT synthesis by MK886, an inhibitor of 5-lipoxygenase-activating protein, reduced the response of Th2 cells to the levels produced by PGD(2) alone. (
  • Immune cells from Peyer's patches were analyzed by Flow Cytometry and toluidine blue staining was used for detection of mast cells. (
  • This was accompanied by an increase in a number of mast cells in the colon of POI mice as well by an increased IgE and histamine plasma levels. (
  • Th2 immune response can be involved in the activation of mast cells in POI, which was associated with ROS mediated activation of NF-κB and p38 MAPK signaling pathway. (
  • To investigate the association between T helper 2 (Th2) cell regulatory and effector molecules' genetic polymorphisms and periodontitis. (
  • The classical view of the Th1/Th2 paradigm posits that the pathogen nature, infectious cycle, and persistence represent key parameters controlling the choice of effector mechanisms operating during an immune response. (
  • Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets. (
  • In this ground-breaking study, his carefully-constructed system allows the migration of T cells to be controlled by light, e.g. attracting more effector T cells into local tumor sites and reducing tumor growth. (
  • Over the course of OIT, we observed suppression of Th2 and Th1 gene signatures in effector clonotypes but not T follicular helper-like (Tfh-like) clonotypes. (
  • However, the mechanism by which IFNγ suppresses Th2 cell proliferation is still not fully understood. (
  • However, cloned Th1 or Th2 cells have a similar capacity to reject skin grafts in experimental models, and Tr1/Treg cells are now being implicated in protection and tolerance induction. (
  • In addition to Th1 and Th2 cells, Th17, Treg and T Fh cells have also been described 7 , Treg cells are associated with reduction of clinical scores of disease in soft and hard tissues 8 . (
  • Usually, protective and destructive roles are assigned to the Th1 and Th17 3,9-11 cells, while Th2 and Treg cells are more involved in processes that reduce the destruction of the periodontium 10 . (
  • CD4+CD25highCD45RA+ "naïve" Treg cells and CD4+CD25highCD45RA- "memory" Treg cells were isolated by FACS (BD FACSAria, BD Biosciences, Heidelberg, Germany) and expanded in vitro. (
  • A subgroup of lymphocytes, helper T cells play an important role in establishing and maximizing the capabilities of the immune system. (
  • Genetic rearrangements occur during the maturation of B lymphocytes, eventually resulting in the surface expression of both immunoglobulin M (IgM) and IgD on mature B cells. (
  • 19. Polarization of T-helper lymphocytes toward the Th2 phenotype in uremic patients. (
  • The inflammatory cells include increased numbers of eosinophils, basophils and T lymphocytes. (
  • Th1 cells are involved in the cellular immune response and host defense against intracellular pathogens. (
  • Th2 cells are involved in the humoral immune response and host defense against extracellular parasites. (
  • Experimental postoperative ileus: is Th2 immune response involved? (
  • Given the impact of reactive oxygen species (ROS) in the regulation of Th1 and Th2 balance, we hypothesized that not only Th1 but also Th2 immune response can be involved in the development of experimental POI. (
  • Recent approaches and applications of new technologies, especially single-cell mRNA analysis in dissecting tumour microenvironments have brought important insights into the biology of tumour-infiltrating immune cells, revealed a remarkable degree of cellular heterogeneity and distinct patterns of immune response. (
  • The aim of this thesis is to assess if IL-10 acts directly or indirectly to promote the type 2 immune response while also suppressing counter-active Th1 cells which provide immune competition. (
  • An allergic inflammatory response is a sequential interaction between various inflammatory and structural cells through their chemical messengers, which together lead to symptoms of allergy. (
  • Depending on the stimulus, the DCs produce CCs including CCL2, CCL3, CCL4, CCL17, CCL22 and CXCL8, thereby leading to the recruitment of various inflammatory cells at the site of allergen exposure. (
  • Understanding these same mechanisms will also help us determine safe upper limits for nutrient intake in the U.S. population, where chronic inflammatory conditions (mediated by both Th2 and Th1 cells) are highly prevalent. (
  • Eosinophils are key immunoeffector and inflammatory cells that have diverse functions, with roles in homeostasis and disease in various tissues. (
  • In COPD, although the major inflammatory cells are CD8 + T cells, neutrophils and macrophages, some patients have eosinophil involvement. (
  • The autoimmune nature of diabetes and inflammatory cytokine IL-10 (as markers the major contribution of lymphocyte T- of inflammatory changes) and the soluble cells are well established. (
  • In allergic asthma, the inflammatory T cells express TH2-like lymphokines [i.e. (
  • Research Objectives and Scope - To elucidate the importance of T cells in the etiology of asthma, the NIAID and the NHLBI are soliciting individual research project grants that are designed to define the role of T cell subsets and their secreted products in the inflammatory processes associated with asthma. (
  • Positive outcomes were associated with stronger suppression of Th2 signatures in Th2A-like cells, while treatment failure was associated with the expression of baseline inflammatory gene signatures that were present in Th1 and Th17 cell populations and unmodulated by OIT. (
  • Thus, our transcriptomic analysis of circulating Th2 cells has identified several molecules that are likely to confer pathogenic features to Th2 cells that are either unique or common to both asthma and rhinitis. (
  • [ 29 ] They form tight junctions with adjacent epithelial cells and detect allergenic molecules without disturbing the epithelial barrier. (
  • Each link will direct you to our product offerings for the study of these cells and molecules. (
  • They can further be subsetted into two predominant types by the expression of other surface molecules, CD4 (CD4+ or helper T cells) and CD8 (CD8+ or cytotoxic T cells). (
  • Molecules that regulate T-cell development by modulating TCR signal strength have been described but components that specifically define the boundaries between positive and negative selection remain unknown. (
  • Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T cell function to promote turmoral immune escape. (
  • Measurement of mast cell surface molecules using high-throughput immunophenotyping using transcription (HIT). (
  • CNM-Au8 is an orally administered suspension made of gold nanocrystals that may protect neurons by raising levels of energy molecules in cells. (
  • To assess T-cell cytokine/chemokine production in clinically stable children with CF and evaluate the association between T-cell subtypes and susceptibility for infection with P. aeruginosa. (
  • Tissue biopsy in Kaposi varicelliform eruption (KVE) shows changes characteristic of herpes virus infection, notably ballooning degeneration of keratinocytes with multinucleated epithelial cells. (
  • 12] A 2008 report noted that depletion of circulating IgD+ memory B cells occurs in pediatric HIV infection, despite control of viral load with highly active anti-retroviral therapy (HAART). (
  • The discovery that CD4 + T cells can be characterized by distinct "cytokine signatures" by Mosmann and Coffman in 1986 ( 1 ) marked the great return of infection in immunology, leading to emergence of the Th1/Th2 "division of labor" paradigm in 1989, and its application to the field of vaccinology since the early 1990s. (
  • Th2 cells produce cy- patients which might reduce the morbidity tokine interleukins IL-4 and IL-10, which and mortality due to infection. (
  • Although CD4 T cells are the main targets of HIV infection, macrophages also become infected and resist the cytopathic effects of infection, contributing potentially to HIV reservoir persistence. (
  • The findings reveal, for the first time, how immune cells work together to get to their final destination - the site of an injury or infection. (
  • Similarly, recognizing how to boost the number of immune cells that travel to fight an infection could help scientists design better vaccines for viruses like the flu. (
  • [ 28 ] DCs extend their processes between the epithelial cells lining the airway lumen or surface. (
  • Healthy and asthmatic participants ages 18 to 70 years may be eligible to participate in this study that seeks to identify enhancers that are important in regulating key airway epithelial cell genes, to determine how enhancer activity changes in asthma, and to develop approaches for targeting the activity of these enhancers. (
  • Th1 cells are centrally involved in cell-mediated immunity. (
  • Although the immune system changes are not well understood, a shift from cell-mediated immunity toward humoral immunity is believed to occur. (
  • Evidence indicates that the maternal immune system may tolerate fetal antigens by suppressing cell-mediated immunity while retaining normal humoral immunity. (
  • Myelomonocytic cells are an essential component of innate immunity and represent the first line of defense against pathogens. (
  • Group 2 innate lymphoid cell activation in the neonatal lung drives type 2 immunity and allergen sensitization. (
  • T Cells in Immunity, Allergic Diseases and Asthma: Latest Advances in NKT Cell and Regulatory T Cell Biology. (
  • Th2 cells are key for the clearance of helminth infections in the SILP. (
  • T-cells have 2 subsets of betic patients with and without nephropathy. (
  • We observed expanded populations of cells expressing Th1, Th2, and Th17 signatures that further separated into 6 clonally distinct subsets. (
  • Four of these subsets demonstrated a convergence of TCR sequences, suggesting antigen-driven T cell fates. (
  • In parallel with the induction of chromatin remodeling, GATA3 mRNA was preferentially expressed in developing Th2 cells, whereas T-bet, HLX and ROG mRNA was selectively expressed in developing Th1 cells. (
  • An immunohistochemical investigation of the gingival tissue was performed to detect the presence of the Th2 specific transcription factor (GATA3). (
  • In vivo blockade of IL-10 led to a significant decrease in IL-13, IL-5 and GATA3 expression by Th2 cells in the intestine and not in the MLN. (
  • In vitro, IL-10 induced expression of GATA3 and production of IL-5 and IL-13 in purified CD4+ T cells. (
  • We found that IFNγ decreases the expression of growth factor independent-1 transcriptional repressor (GFI1) in Th2 cells, resulting in the inhibition of Th2 cell proliferation. (
  • These results demonstrate that GFI1 is a key molecule in the IFNγ-mediated inhibition of Th2 cell proliferation. (
  • Notably, however, the establishment of fundamental immunological concepts and paradigms, such as B and T cell collaboration or tolerance, was based on a reductionist (or analytical) approach that departed from a classical "host-pathogen" view of immunology, by putting much emphasis on self/non-self discrimination concepts explored with simpler protein antigens such as ovalbumin or keyhole limpet hemocyanin (KLH). (
  • Because Th2 cells play a pathogenic role in both these diseases and are also present in healthy nonallergic subjects, we performed global transcriptional profiling to determine whether there are qualitative differences in Th2 cells from subjects with allergic asthma, rhinitis, and healthy controls. (
  • Several genes that oppose T cell activation were downregulated in asthma, suggesting enhanced activation potential of Th2 cells from asthmatic subjects. (
  • This Program Announcement, Asthma as a T-cell-mediated Disease, is related to the priority area of diabetes and chronic disabling diseases. (
  • o Determination of the effects on T-cell populations of agents useful in treatment of allergic diseases and asthma, such as allergen immunotherapy and glucocorticosteroids. (
  • Methods: Dendritic cells were derived from mouse bone marrow, and their expression of the IL-33 receptor, ST2, was examined by fluorescence-activated cell sorting and real-time RT-PCR. (
  • Conclusion: Dendritic cells respond directly to IL-33 through ST2. (
  • The deletion of the Gfi1 gene in Th2 cells results in the failure of their proliferation, accompanied by an impaired cell cycle progression. (
  • In contrast, the enforced expression of GFI1 restores the defective Th2 cell proliferation, even in the presence of IFNγ. (
  • Of recent interest have been immune checkpoint inhibitors targeting T cell receptors, such as PD-1 and CTLA-4, which have been successful in un-inhibiting T cell activation and proliferation of antigen-experienced T cells in the tumor microenvironment. (
  • and promotes mast cell proliferation in combination with IL-4. (
  • 9. Atorvastatin modulates Th1/Th2 response in patients with chronic heart failure. (
  • Th2/1 cells differentiated from naive precursors and accumulated in spleen and intestine of infected mice, resulting in increased systemic and mucosal IFN-γ production. (
  • Studies in IgM-deficient IgM-/- mice reveal that B cells with surface expression of IgM were replaced by B cells with surface expression of IgD. (
  • Th1/Th2 Paradigm Extended: Macrophage Polarization as an Unappreciated Pathogen-Driven Escape Mechanism? (
  • Pathogen-associated molecular patterns of allergens are recognized by Toll-like receptors (TLRs) on DCs, which initiate their maturation and augment their homing by upregulating CC receptors, which then direct them towards the T-cell zone of the lymph nodes. (
  • From 1990 to 2010, he mainly worked on natural killer (NK) cell receptors for MHC class I and regulation of NK cell functions and development. (
  • Integrins, a family of membrane receptors, are expressed in all different types of cells in human body and regul. (
  • Integrins, a family of membrane receptors, are expressed in all different types of cells in human body and regulate important cell adhesion and migration. (
  • However, when combined with PGD(2), cysLTs caused a greater than additive enhancement of the response, with LTE(4) being most effective in activating Th2 cells. (
  • LTE(4) enhanced calcium mobilization in response to PGD(2) in Th2 cells without affecting endogenous PGD(2) production or CRTH2 receptor expression. (
  • 2 Chimeric antigen receptor (CAR)-T cells, such as anti-CD19 CAR-T cells, have been extremely successful (approximately 93% response) against B cell malignancies, such as acute lymphoblastic leukemia. (
  • Murine Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations. (
  • Conclusions: These results indicate that the Th2 response may have a protective role during the pathogenesis of experimental periodontal disease, and that the IFN-γ R1 subunit may not be associated with periodontal disease progression. (
  • This increased expression seemed to be associated with a Th2 response. (
  • Our results indicate that Shn2 −/− double-positive thymocytes inappropriately undergo negative selection in response to positive selecting signals, thus leading to disrupted T-cell development. (
  • The outcome of immune checkpoint inhibitors in cancer patients has been linked to the quality and magnitude of T cell, NK cell, and more recently, B cell within the tumour microenvironment, suggesting that the immune landscape of a tumour is highly connected to patient response and prognosis. (
  • In typical individuals, the chromatin remodeling indicated by the induction of hyper-acetylation of histone H3 lysine 9 and hyper-methylation of histone H3 lysine 4 was induced at the whole Th2 cytokine gene loci in developing Th2 cells. (
  • Subversion of macrophage cell metabolism by microbes appears as a recently uncovered immune escape strategy. (
  • T cells originate in the bone marrow and travel to the thymus for their maturation. (
  • Click on the tabs below for flow cytometry phenotyping suggestions and extended lists of secreted, cell surface, and intracellular markers. (
  • Interestingly, in addition to represent immune effectors, M1/M2 cells have been shown to represent potential reservoir cells to a wide range of intracellular pathogens. (
  • Early in his career, Dr. Kim developed a highly innovative bio-imaging assay using FRET (Fluorescence Resonance Energy Transfer) techniques and show for the first time in live cells that the intracellular domains of integrin LFA-1 moved apart substantially during immune cell migration, and his paper describing this (Kim et al. (
  • The fluorochrome-labeled JES5-16E3 antibody is useful for intracellular immunofluorescent staining and flow cytometric analysis to identify IL-10-producing cells within mixed cell populations. (
  • Here we demonstrate Th2/1 cells as the major source of parasite-specific IFN-γ production in acute and chronic infections with the enteric nematode Heligmosomoides polygyrus. (
  • Diabetic nephropathy (DN) is a leading selectin), and soluble thrombomodulin--are cause of chronic renal failure and is a grow- providing further evidence of the relation- ing concern given the increasing incidence ship between endothelial cell activation and of type 2 diabetes. (
  • This system allowed us to investigate the chromatin status at the Th2 cytokine gene loci and the IFNγ locus in human Th2 and Th1 cells, respectively. (
  • We more precisely assessed the methylation status of histone H3 lysine 4 at the Th2 cytokine gene loci (IL-5 exon 3, IL-5 promoter, IL-5/RAD50 intergenic region, RAD50 promoter, CGRE, CNS1, IL-13 promoter, IL-4 promoter, and V A enhancer regions) and the IFNγ locus in developing Th1 and Th2 cells prepared from 20 healthy volunteers. (
  • Th2-cell specific chromatin remodeling was induced at most of the Th2 cytokine gene loci. (
  • Mechanics of T cell receptor gene rearrangement. (
  • We propose that RXR-mediated transcription from specific genes is required for normal Th2 development. (
  • 7. Time-dependent cytokine deviation toward the Th2 side in Japanese multiple sclerosis patients with interferon beta-1b. (
  • We have recently found that stimulation of the retinoid X receptor (RXR) pathway in antigen-naive Th0 cells promotes development of Th2 memory cells (as indicated by the production of IL-4), while stimulation of the retinoic acid receptor (RAR) pathway does not. (
  • 8. Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in women with multiple sclerosis. (
  • These so-called Th9 cells can differentiate from Th2 cells in the presence of TGF-β or they can differentiate from a naïve CD4 cell with a combination of IL-4 and TGF-β. (
  • In order to differentiate into Th1 or Th2 cells, CD4 T cells must become antigen-activated. (
  • Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. (
  • 14. Depressed interleukin-12-producing activity by monocytes correlates with adverse clinical course and a shift toward Th2-type lymphocyte pattern in severely injured male trauma patients. (
  • In 2010, he found a unique lymphocyte population, which is now termed group 2 innate lymphoid cell (ILC2), in mouse lungs. (
  • Generation of a diverse and self-tolerant T-cell repertoire requires appropriate interpretation of T-cell antigen receptor (TCR) signals by CD4 + CD8 + double-positive thymocytes. (
  • These findings reveal that cysLTs, in particular LTE(4), have a significant proinflammatory impact on T cells and demonstrate their effects on Th2 cells are mediated by a montelukast-sensitive receptor. (
  • This leads to crosslinking of the IgE-FcRI complex, which then triggers activation of these cells and release of substances causing symptoms of allergy. (
  • The high affinity of FcRI for IgE facilitates rapid IgE-FcRI interaction, a step critical for IgE-mediated mast cell activation. (
  • In contrast, Lck-deficient cells expressed constitutively elevated levels of lymphokine mRNA, including IL-4, IL-5, and IL-10, and were capable of secreting IL-4 upon activation through the TCR. (
  • In fibrotic scenarios, immune cells are activated including varying immune pathways, ranging from innate immune cell activation to autoimmune disease. (
  • Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. (