• iNKT cells have been traditionally defined by the expression of an invariant TCR α-chain (Vα14-Jα18 in mice or Vα24-Jα18 in humans) and their capacity to recognise the glycolipid antigen α-galactosylceramide (αGalCer) presented on CD1d. (elifesciences.org)
  • NKT cells, through TCR recognition of self- or commensal-derived lipids presented by CD1d, contribute to establish immune homeostasis and to anti-microbial, anti-tumour and autoimmune responses (10,11). (europa.eu)
  • α-GalCer is a potent activator of iNKT cells, and a model CD1d antigen. (wikipedia.org)
  • The invariant T cell receptor of the iNKT cell is able to bind the CD1d:glycolipid complex leading to iNKT cell activation in both mice and humans. (wikipedia.org)
  • The CD1d:glycolipid:TCR interaction activates the iNKT cell which can then activate the dendritic cell. (wikipedia.org)
  • The adipocyte was reported as an antigen-presenting cell (APC) which expresses CD1d and MHC class I and II molecules. (frontiersin.org)
  • Several studies have shown that adipocytes highly express CD1d, which presents lipid antigens to invariant natural killer T (iNKT) cells and stimulates the activation of iNKT cells ( 5 - 7 ). (frontiersin.org)
  • iNKT cells can recognize endogenous lipids presented by CD1d molecules on tumor cells and release Perforin and Granzyme B to lyse tumor cells directly. (aacrjournals.org)
  • In the absence of CD1d expression on tumor cells, iNKT cells may become activated in response to CD1d-expressing or Toll-like receptor (TLR)-activated antigen-presenting cells (APC). (aacrjournals.org)
  • Dr. Cerundolo demonstrated how the length and saturation of lipid antigens contained within the CD1d binding site modulate their affinity of binding to invariant NKT cells (iNKT cells), hence explaining how lipid-specific lymphocytes are capable of recognizing both the group head and the length of lipid antigens, ensuring greater specificity of antigen recognition. (aacrjournals.org)
  • His seminal findings on the processing and presentation of peptide and lipid antigens made fundamental advances to the field of antigen presentation to MHC class I-restricted T cells and CD1d-restricted iNKT cells. (aacrjournals.org)
  • CD1d-restricted invariant natural killer T (iNKT) cells actively participate in tumor immunosurveillance by restricting suppressive myeloid populations in the TME. (unimib.it)
  • Here, we showed that harnessing iNKT cells with a second TCR specific for a tumor-associated peptide generated bispecific effectors for CD1d- and major histocompatibility complex (MHC)-restricted antigens in vitro. (unimib.it)
  • Invariant natural killer T (iNKT) cells are CD1d-restricted T cells, which respond rapidly to antigen recognition and promote development of anti-tumor immunity in many tumor models. (biomedcentral.com)
  • The effects of antibody-mediated blockade of CD1d on DC number and phenotype, priming of anti-tumor T cells, and tumor response to treatment with local radiotherapy and anti-CTLA-4 antibody were evaluated. (biomedcentral.com)
  • CD1d blockade restored the number of DC in WT mice, improved T cell priming in draining lymph nodes and significantly enhanced response to treatment. (biomedcentral.com)
  • Although initially identified by co-expression of conventional αβ T-cell receptors (TCR) and markers typically associated with natural killer (NK) cells [ 3 ], NKT are currently distinguished on the basis of CD1d restriction as well as specific usage of TCRα chains [ 4 ]. (biomedcentral.com)
  • Here we report that endoplasmic reticulum (ER)-stressed myeloid cells, via signaling events modulated by the protein kinase RNA-like ER kinase (PERK) pathway, increase CD1d-mediated presentation of immunogenic endogenous lipid species, which results in enhanced iNKT cell activation both in vitro and in vivo. (ox.ac.uk)
  • In addition, we demonstrate that actin cytoskeletal reorganization during ER stress results in an altered distribution of CD1d on the cell surface, which contributes to enhanced iNKT cell activation. (ox.ac.uk)
  • Recognition of lipid-based antigens presented by CD1d sets iNKT cells apart from conventional T cells. (guidetomalariapharmacology.org)
  • GC) and delineate the mechanisms of action with a particular emphasis on CD1d-restricted Natural Killer T (NKT) cells and humoral immunity. (grantome.com)
  • GC leads to CD1d/glycolipid presentation and a coordinated dNKT and iNKT- driven mixed Th1/Th2 response against vaccine antigens. (grantome.com)
  • In Specific Aim 1, we will perform a series of in vitro studies in primary murine and human cells to determine how the adjuvant combination affects CD1d Ag presentation and activation and functional differentiation of NKT cells into different effector subsets. (grantome.com)
  • We feel this project is innovative because it will provide the vaccine community with mechanistic information when CD1d-binding adjuvants are combined with Alum adjuvant and give careful consideration to NKT cell- driven components of the immune response. (grantome.com)
  • They are unique in their restriction to lipid antigens presented in CD1d molecules, which underlies their role in lipid-driven disorders such as obesity and atherosclerosis. (ox.ac.uk)
  • Invariant natural killer T (iNKT) cells are a specialised subset of T cells that are restricted to the MHC class I like molecule, CD1d. (ox.ac.uk)
  • Trafficking of CD1d through the lysosome is required for the development of murine iNKT cells. (ox.ac.uk)
  • In the NPC1 mouse model, iNKT cells are virtually undetectable, which is likely due to the inability of CD1d to be loaded with the selecting ligand due to defective lysosomal function and/or CD1d trafficking. (ox.ac.uk)
  • In addi-tion, antigen-presenting cells derived from NPC1 patients are functionally competent to present several different CD1d/iNKT-cell ligands. (ox.ac.uk)
  • Many hematopoietic cell types express CD1d and so are with the capacity of presenting glycolipid antigens to invariant natural killer T?cells (iNKT cells). (biotech-angels.com)
  • Graphical Abstract Introduction Natural killer T?cells with invariant T?cell receptor α chains (iNKT cells) are a conserved population that recognizes KM 11060 glycolipid antigens bound to CD1d a lipid antigen-presenting molecule with structural similarities to major histocompatibility complex (MHC) class I proteins (Brennan et?al. (biotech-angels.com)
  • 2011 A unifying feature of αGC analogs that induce predominantly Th2 cell-associated cytokines is that they are more polar than KRN7000 and can load directly onto CD1d molecules on the cell surface (Im et?al. (biotech-angels.com)
  • 2011 In contrast glycolipids that induce responses that are biased toward Th1 cell cytokines are more hydrophobic and require intracellular loading onto CD1d for presentation (Arora et?al. (biotech-angels.com)
  • 2009 Because most cells of hematopoietic origin express CD1d (Brossay et?al. (biotech-angels.com)
  • 2012 However other studies yielded different conclusions identifying pharmacokinetic properties of the glycolipids or localization of CD1d molecules containing bound glycolipids to different membrane microdomains as major determinants of cytokine skewing in the response to iNKT cell activation (Im et?al. (biotech-angels.com)
  • By visualizing glycolipid antigen presentation directly with monoclonal antibodies specific for complexes of αGC bound to CD1d we showed that the CD8α+DEC-205+ subset of dendritic cells was the major APC in the spleen for a range of αGC analogs irrespective of their chemical structures and cytokine biasing activities. (biotech-angels.com)
  • iNKT cells were analyzed for CD1d PBS57 tetramer reactivity. (clinical-research-informatics.com)
  • Along these same lines, the lab uses innovative approaches to direct iNKT cells to the site of cancers in a tumor antigen-specific yet CD1d-independent manner. (msu.edu)
  • Cell surface receptors containing an immunoglobin domain. (embl.de)
  • Killer cell inhibitory receptors. (embl.de)
  • Histamine and its receptors represent a complex system of immunoregulation with distinct effects mediated by four GPCRs (G protein-coupled receptors HRs 1-4) and their differential expression, which changes according to the stage of cell differentiation and microenvironmental influences. (hindawi.com)
  • Adoptive immunotherapy with T cells engineered with tumor-specific T cell receptors (TCRs) holds promise for cancer treatment. (unimib.it)
  • opposing effects of activating and inhibitory receptors regulate NK cell activity. (mhmedical.com)
  • Surprisingly the induction of Th1 cell- versus Th2 cell-associated cytokines and the extent of NK cell transactivation do not correlate consistently with the potency of different αGC analogs or with the affinity with which they interact with the T?cell receptors (TCRs) of iNKT cells (Im et?al. (biotech-angels.com)
  • This suggests that unique tissue-specific factors (including local lipid antigens, cytokines and/or hormones) may shape the population of iNKT cells resident in those tissues, ultimately regulating local immune responses. (elifesciences.org)
  • This causes the release of a range of cytokines and licenses the dendritic cell to activate a peptide-specific T cell response. (wikipedia.org)
  • Next, we summarize various cytokines produced by adipocytes that regulate the survival, activation and differentiation of B cells. (frontiersin.org)
  • In this review, we discuss the dualistic effects of histamine: how histamine affects inflammation of the immune system through the activation of intracellular pathways that induce the production of inflammatory mediators and cytokines in different immune cells and how histamine exerts regulatory functions in innate and adaptive immune responses. (hindawi.com)
  • Natural killer (NK) cells, with a predominant morphology of large granular lymphocytes, represent a lineage of lymphoid cells with constitutive ability to mediate cytotoxicity toward pathologic target cells and secrete cytokines. (mhmedical.com)
  • iNKT cells can promote the polarization of adaptive immune responses towards both Th1 and Th2 and can secrete immunosuppressive cytokines [ 19 ]. (biomedcentral.com)
  • Since KRN7000 stimulates iNKT cells to release both Th1 and Th2 cytokines in relative amounts at which the biological activity of either one is antagonized by the other, tremendous effort has been devoted toward synthesizing analogues of KRN7000 that bias cytokine release, as such targets may offer new approaches to treating viral infections, bacterial infections, cancer, and autoimmune conditions. (uconn.edu)
  • This anastomotic study demonstrated a decrease in IEC TLR4 expression and microbiome diversity which then coincided with increased expansion of regulatory and pro-inflammatory immune cells and cytokines. (biomedcentral.com)
  • Third, external signals such as toll-like receptor ligands, adipokines, and cytokines modulate antigen presentation and subsequent iNKT cell responses. (ox.ac.uk)
  • 2008 Multiple studies show that this transactivation is influenced by the precise structure of glycolipid antigens which has enabled manipulation of immune responses with structural analogs of αGC (Venkataswamy and Porcelli 2010 For example derivatives of αGC containing truncated or unsaturated N-acyl chains induce responses in which cytokines typically associated with T helper-2 (Th2) cells predominate KM 11060 and transactivation of NK cells is limited (Yu et?al. (biotech-angels.com)
  • 2005 On the other hand replacing the O-glycosidic linkage of αGC with a nonhydrolyzable carbon linker gives a C-glycoside variant that induces cytokine responses biased toward cytokines characteristic of T helper 1 (Th1) cells along with enhanced transactivation of NK cells and their secretion of interferon-γ (IFN-γ) (Schmieg et?al. (biotech-angels.com)
  • By analysing iNKT cells from lymphoid tissues of mice and humans we demonstrate that their T cell receptor (TCR) repertoire is highly diverse and is distinct for cells from various tissues resulting in differential lipid-antigen recognition. (elifesciences.org)
  • Translational Candidate A single-chain bispecific chimeric antigen receptor (CAR) targeting BCMA and CS1 will be used to in autologous T-cell therapy for multiple myeloma. (ca.gov)
  • Human iPSC-derived chimeric antigen receptor expressing macrophages for improved cancer treatment. (ca.gov)
  • However, the impact of iNKT cell receptor β-chain repertoire and how α-galactosylceramide (α-GalCer) analogues induce distinct functional responses have remained elusive. (ox.ac.uk)
  • iNKT cell proliferation and cytokine secretion, which correlate with iNKT cell receptor down-regulation, are induced within narrow biochemical thresholds. (ox.ac.uk)
  • Multimers of CD1d1-αGalCer- and αGalCer analogue-loaded complexes demonstrate cooperative engagement of the Va14Ja18 iNKT cell receptor whose structure and/ or organization appear distinct from conventional αβ TCR. (ox.ac.uk)
  • Our findings demonstrate that iNKT cell functions are controlled by affinity thresholds for glycolipid Ags and reveal a novel property of their Ag receptor apparatus that may have an important role in iNKT cell activation. (ox.ac.uk)
  • iNKT cells constitutively express high levels of Nr4a1-encoded Nur77, a transcription factor that integrates signal strength downstream of the T cell receptor (TCR) within activated thymocytes and peripheral T cells. (ox.ac.uk)
  • Laukkanen et Bopindolol malonate al [2] discovered that adenovirus-mediated gene transfer of the secreted type of individual macrophage scavenger receptor (SR) inhibited customized LDL degradation and foam-cell formation in macrophages. (techblessing.com)
  • Furthermore Siglec-1 on macrophage can serve as receptor for a few pathogen and facilitate pathogen infection Bopindolol malonate of web host cells [8] [9]. (techblessing.com)
  • CRTH2: Chemoattractant receptor-homologous molecule expressed includes nonallergic asthma phenotypes, such as asthma on TH2 cells associated with exposure to air pollution, infection, or obesity, ILC: Innate lymphoid cell that require innate rather than adaptive immunity. (cdc.gov)
  • pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD. (molcells.org)
  • B ) Muzzle skin was digested and analyzed via FACS for Siglec F + eosinophils (left panels), Ly- 6G + neutrophils (middle panels), Ly-6C + MHC-II lo monocytes and Ly-6C + MHC-II hi monocyte-derived dendritic cells (right panels). (elifesciences.org)
  • The innate immune system includes macrophages, dendritic cells (DC), and natural killer (NK) cells, which respond quickly to an immunological threat. (nature.com)
  • agenT-797 activates dendritic cells, which can promote activation of T cells through enhanced antigen presentation. (advfn.com)
  • To understand the mechanisms of the immunosuppressive function of iNKT cells, dendritic cells (DCs) were analyzed by immunohistochemistry and flow cytometry in WT and iNKT-deficient (iNKT −/− ) mice. (biomedcentral.com)
  • We will also analyze the peptides presented by dendritic cells from healthy donors expressing T1D-associated HLA alleles pulsed with b-cells protein extracts and/or soluble autoantigens. (uab.cat)
  • T-cells are studied by i) molecular and functional level, ii) TCR diversity and clonality and iii) peptide repertoire presented by dendritic cells pulsed with tumor tissue. (uab.cat)
  • A phase I-II clinical study of αGalCer-pulsed dendritic cells (DC) to activate endogenous iNKT cells was previously performed in patients with non-small-cell lung cancer (NSCLC). (elsevierpure.com)
  • This occurs both through KM 11060 direct stimulation of iNKT cell functions and by transactivation of other effectors most notably NK cells and dendritic cells (Brennan et?al. (biotech-angels.com)
  • Interaction of CD8α+ dendritic cells (DCs) with iNKT cells during presentation of Th1 cell-biasing versus Th2 cell-biasing glycolipid antigens led to markedly different changes in expression of costimulatory and coinhibitory molecules on these. (biotech-angels.com)
  • OBJECTIVE: The role of plasmacytoid dendritic cells (PDCs) and type I interferons (IFNs) in rheumatoid arthritis (RA) remains a subject of controversy. (cnrs.fr)
  • 2003 Several models have been put forth to explain how variations in the structure of glycolipid antigens lead to different outcomes of iNKT cell activation. (biotech-angels.com)
  • 1997 it has been proposed that selective presentation by different cell types could account for variation in functional outcomes with different glycolipid antigens (Bezbradica et?al. (biotech-angels.com)
  • 2010 In the current study we reassessed the presentation of various forms DUSP2 of αGC in?vivo to identify the predominant APCs involved in presentation of diverse glycolipid antigens. (biotech-angels.com)
  • Tissue homeostasis is critically dependent on the function of tissue-resident lymphocytes, including lipid-reactive invariant natural killer T (iNKT) cells. (elifesciences.org)
  • Invariant natural killer T (iNKT) cells are a unique population of T lymphocytes that lies at the interface between the innate and adaptive immune systems, and they are important mediators of immune responses and tumor surveillance. (aacrjournals.org)
  • Natural killer T (NKT) cells comprise a subset of lymphocytes originating from a distinct developmental lineage [ 1 ] which bridge innate and adaptive immunity and modulate immune responses in autoimmunity, malignancies and infections [ 2 ]. (biomedcentral.com)
  • Although immunotherapy is an alternative to a large number of diseases mediated by the immune system, the use of specific agonists to the invariant Natural Killer T (iNKT) lymphocytes remains neglected.One of these antagonists, the alfa-Galactosylceramide (a-GalCer), has been used in clinical trials, however, despite positive results, its efficiency is underwhelming. (fapesp.br)
  • Semi-invariant natural killer T (iNKT) cells are self-reactive lymphocytes, yet how this lineage attains self-tolerance remains unknown. (ox.ac.uk)
  • Our previous works revealed that within the immune system, the target-cells of the regulatory effects of TGF-β are T lymphocytes (Immunity 2006) and that TGF-β signaling represses their activation against self-cells. (crcl.fr)
  • Since iNKT cell activation can prevent or promote immunopathology in diverse disease contexts, the strict control of peripheral iNKT cell homeostasis is vital to regulate local immunity. (elifesciences.org)
  • Beyond the common features shared by all iNKT cells (including their CD1-restriction and innate-like properties), cells found in discrete tissues have distinct phenotypes and functions that critically modulate the outcome of immunity ( Crosby and Kronenberg, 2018 ). (elifesciences.org)
  • Taking this into consideration, this project has focussed in understanding the mechanisms controlling lipid-mediated immunity by examining the ILC-NKT cell crosstalk. (europa.eu)
  • As mentioned above, the project aimed to investigate the mechanisms regulating lipid-mediated immunity in the intestinal mucosa by examining the crosstalk between ILCs and NKT cells. (europa.eu)
  • The adaptive immune response consists of T cell-mediated cellular immunity and B cell-mediated humoral immunity. (frontiersin.org)
  • Therefore, adipocytes play an important role in B cell-mediated adaptive immunity. (frontiersin.org)
  • This review describes how adipocytes participate in adaptive immunity from the perspective of T cells and B cells, and discusses their role in the pathogenesis of various diseases. (frontiersin.org)
  • There are two main mechanisms in the adaptive immune system-humoral immunity and cellular immunity, which are mediated by antibodies and cells respectively. (frontiersin.org)
  • The T and B cells are the major components of adaptive immunity. (frontiersin.org)
  • Research Objective We propose to generate NK cells with enhanced immunity from gene-edited human PSCs and use the resultant NK cells to kill SARS-CoV-2-infected cells to combat against COVID-19. (ca.gov)
  • 1 , 2 NK cells are now considered to belong to the cellular subgroup that is characterized by the production of interferon (IFN)- γ within the family of innate lymphoid cells (ILCs), a family of developmentally related cells involved in innate immunity and tissue development. (mhmedical.com)
  • Invariant NKT (iNKT) cells have the unique ability to shape immunity during antitumor immune responses and other forms of sterile and nonsterile inflammation. (ox.ac.uk)
  • We reported that TGF-β influences the thymus negative selection (Nature Com 2019) the differentiation of memory T cells (Nature Com 2014, Immunity 2012), NKT (J. Exp Med 2009, Blood 2012) and Treg stability and function (J.Exp Med 2005, Immunity 2015, Nature Immunol 2020). (crcl.fr)
  • Within the tumor TGF-b is a key cytokine controlling the cytotoxic functions of CD8 T cells ( Immunity 2006, cancer research 2020) Our lab developed several innovative tools to study both cellular and molecular mechanisms responsible for the control of peripheral T cell tolerance to self-cells by TGF-β with direct consequences on autoimmunity, inflammation and tumor development. (crcl.fr)
  • This research contributes to an understanding of iNKT cell biology and will help identify how the cytotoxic function of these cells could be enhanced to augment host immunity to cancer. (msu.edu)
  • The Lymphocyte Interaction Laboratory was the first team to establish a role for a group of macrophages in acquiring antigen and presenting intact antigen to follicular B cells in lymph nodes in vivo . (labbulletin.com)
  • Now, they have identified a novel role for CD169+ macrophages in activating Invariant Natural Killer T (iNKT) cells. (labbulletin.com)
  • Imaris was also able to demonstrate the confinement of the iNKT cells in the vicinity of the CD169+ macrophages following administration of particulate lipid antigen by reconstructing the lymph nodes in three dimensions. (labbulletin.com)
  • In these studies, the research team successfully used Imaris to visualize the long-standing interactions between CD169+ macrophages and iNKT cells and found very fast iNKT activation and cytokine secretion. (labbulletin.com)
  • Siglec-1(+) macrophages can internalize lipid antigen and procedure and present it to iNKT cells leading to T cells proliferation and activation [7]. (techblessing.com)
  • First, we outline the role of iNKT cells in immunometabolic disease. (ox.ac.uk)
  • Despite this prototypical TCR repertoire gene usage, in recent years it has become apparent that there are variations within the iNKT cell repertoire that ultimately impact the antigen recognition capacity and consequently the functional outcomes during an immune response. (elifesciences.org)
  • Using altered glycolipid ligands, we discovered that the Vb repertoire of iNKT cells impacts recognition and Ag avidity, and that stimulation with suboptimal avidity Ag results in preferential expansion of high-affinity iNKT cells. (ox.ac.uk)
  • Respect to the recognition of proteins by T cells, our approach, following our previous experience with T1D and other autoinmune diseases, is to find T cell ligands that are present in the periphery but are not found in the thymus. (uab.cat)
  • T cell reactivity to the identified natural ligands will be screened. (uab.cat)
  • However, the target ligands recognized by these cells in the autoimmune context are barely known. (uab.cat)
  • Further, little is known about local lipid ligands for NKT cells that may be influencing the disease outcome. (uab.cat)
  • The ligands for iNKT cells are lipids, with the canonical superagonist being α-galactosylceramide, a non-mammalian glycosphingolipid. (ox.ac.uk)
  • Apart from proteins, lipid-based antigens can load on MHC-I non-classical CD1 molecules and be recognized by NKT cells. (uab.cat)
  • Consistent with this, iNKT cells from different organs show distinct basal activation, proliferation and clonal expansion. (elifesciences.org)
  • Sphingolipids are an extensive class of lipids with different functions in the cell, ranging from proliferation to cell death. (frontiersin.org)
  • In addition, various adipokines secreted by adipocytes regulate the proliferation and differentiation of T cells. (frontiersin.org)
  • Sphingolipids are remarkably diverse and have crucial roles in maintaining barrier function and fluidity, as well as regulating the cell cycle, cell motility, differentiation, adhesion, and apoptosis ( 1 ). (frontiersin.org)
  • Nur77 controls tolerance induction, terminal differentiation, and effector functions in semi-invariant natural killer T cells. (ox.ac.uk)
  • Thus, Nur77 integrates signals emanating from the TCR to control thymic iNKT cell tolerance induction, terminal differentiation, and effector functions. (ox.ac.uk)
  • that regulate the differentiation and activation of these cells. (cdc.gov)
  • We also revealed that TGF-β prevents from autoantibody development by regulating T follicular heper cells differentiation (J. Clin Invest 2014). (crcl.fr)
  • Constitutive CD8 expression drives innate CD8+ T-cell differentiation via induction of iNKT2 cells. (illumina.com)
  • One of these cell types is the population called innate lymphoid cells (ILCs) which comprise several families of cells that can be classified into three groups: ILC type 1 (ILC1), ILC2 and ILC3. (europa.eu)
  • Furthermore, other cells at the interface of the innate and the adaptive immune system (e.g cytokine-induced killer cells (CIK) or invariant natural killer T-cells (iNKT)) are important mediators in antitumor-, autoimmune-, and antimicrobial responses and tumor surveillance. (nature.com)
  • Furthermore, we aimed to investigate if the induced innate immune responses before initiation of cART were associated with CD4+ T-cell recovery one year after initiating cART. (bvsalud.org)
  • The induced innate immune responses before cART initiation were not associated with the CD4+ T-cell recovery after 12 months of cART. (bvsalud.org)
  • Conclusion: The innate immune response was impaired in PWH, with a more pronounced impairment in PWH with low nadir CD4+ T-cell count. (bvsalud.org)
  • Our iNKT engagers, PORT-2 and PORT-3, lead to a broad reprogramming of the innate and adaptive immune system, enabling the body to recognize and attack tumors that contain few immune cells and usually go undetected. (portagebiotech.com)
  • Rafael is studying the shared mechanisms underlying the 'poised' innate phenotype in effector T cell populations including iNKT cells, MAIT cells, γδ T cell and NK cells. (harvard.edu)
  • IL-8) and chemokines that recruit innate and adaptive immune cells to limit bacterial invasion. (biomedcentral.com)
  • 1. To be able to describe the role of innate lymphoid cells (ILCs) in Date of Original Release: April 2014. (cdc.gov)
  • NKT: Natural killer T innate lymphoid cells and their role in asthma. (cdc.gov)
  • The Das Lab examines signaling mechanisms that regulating the function of conventional and innate type T cells. (msu.edu)
  • In addition to their direct anti-tumor activity, allogeneic iNKT cells (agenT-797) improve immune effector function of immune cells in the tumor microenvironment. (advfn.com)
  • PORT-2 is a small molecule iNKT engager (IMM60) packaged in a liposome, which optimally activates multiple components of the immune response and inhibits negative signals in the tumor microenvironment. (portagebiotech.com)
  • Obese adipocytes overexpress MHC class II molecules and costimulators to act as antigen-presenting cells (APCs) and promote the activation of CD4 + T cells. (frontiersin.org)
  • Moreover, like other nucleated cells, adipocytes express MHC class I molecules. (frontiersin.org)
  • We are aiming at the ex vivo identification of peptides presented by MHC class I and class II molecules from pancreatic b cells and thymus from donors matching relevant MHC class I and II alleles. (uab.cat)
  • Data_Sheet_1.pdf (513K) GUID:?514B8128-1B6A-4BCF-ADFD-8945AF1CB772 Abstract The lysosome has a key role in the presentation of lipid antigens by CD1 molecules. (clinical-research-informatics.com)
  • Immune checkpoints transient third-degree atrioventricular block, and are costimulatory and coinhibitory molecules usually a right hemicorporeal clonic seizure, after which expressed on the surface of immune cells and modu- mental status was persistently altered. (cdc.gov)
  • Within peripheral tissues iNKT cell recent thymic emigrants exhibit a different TCR repertoire than mature cells, suggesting that the iNKT population is shaped after arrival to the periphery. (elifesciences.org)
  • Searching for the b cell-specific peptides identified in the thymic medulla. (uab.cat)
  • iNKT cells in bone marrow chimeras that reconstituted thymic cellularity developed beyond stage 0 precursors and yielded IL-4-producing NKT2 cell subset but not IFN-γ-producing NKT1 cell subset. (ox.ac.uk)
  • Nonetheless, the developing thymic iNKT cells that emerged in these chimeras expressed the exhaustion marker PD1 and responded poorly to a strong glycolipid agonist. (ox.ac.uk)
  • Both ILC2 and ILC3 populations are able to internalize and present peptide antigens on MHC-II and control T cell responses (3-7). (europa.eu)
  • PORT-3 is a nanoparticle co-formulation of the iNKT engager IMM60 and NY-ESO-1 peptide antigens. (portagebiotech.com)
  • Dr. Cerundolo described the first human antigen processing-deficient cells, leading to the cloning and characterization of the transporter associated with antigen-processing 1 and 2 (TAP1, TAP2) genes and the identification of several families of TAP1/2-deficient patients with necrotizing granulomatous skin lesions and small vessel vasculitis. (aacrjournals.org)
  • Specific loss of Vγ2 + Tγδ17 cells, scratching behaviors and reciprocally enhanced effector function of ILCs in Sox13 -/- mice with dermatitis. (elifesciences.org)
  • Va14Ja18 natural T (iNKT) cells rapidly elicit a robust effector response to different glycolipid Ags, with distinct functional outcomes. (ox.ac.uk)
  • Much less is known on CD4+ effector or regulatory T cell recognized peptides in human T1D. (uab.cat)
  • NKT cells regulate effector T cells in an IL13 dependent manner. (uab.cat)
  • Currently, she is studying the role of prostaglandin production by human T cells in regulating Th2 effector functions. (harvard.edu)
  • She is studying novel Th2 effector pathways uncovered using single-cell RNA-seq from human tissue. (harvard.edu)
  • 2012 Studies of the prototypical glycolipid antigen of iNKT cells an α-galactosylceramide (αGC) known as KRN7000 show the potential for iNKT cells to KM 11060 activate a range of immune effector functions in?vivo. (biotech-angels.com)
  • G ) Muzzle-infiltrating cells were isolated from LMC and Sox13 -/- mice and re-stimulated in vitro with PdBu/ionomycin to assess production of IL-5 and IL-13 by ILCs. (elifesciences.org)
  • H ) Increased skin γδ T cells, including Tγδ17 cells (TCRδ int ), in 4-6 week old Rora -/- mice. (elifesciences.org)
  • Aberrant αβ T cell activation in AD of Sox13 -/- mice. (elifesciences.org)
  • A ) Total number of the indicated T cell types recovered from skin of from 5-6mo mice were calculated using AccuCheck counting beads. (elifesciences.org)
  • B ) FACS analysis of CD4 neg CD8β neg skin T cells (gated on B220 - F4/80 - TCRβ + ) with control MR1/6-FP or MR1/5-OP-RU tetramer to identify MAIT cells in 5 mo mice. (elifesciences.org)
  • C ) Summary data of frequency of MAIT tetramer-reactive cells among total TCRβ + cells pooled from two independent experiments, performed as in Panel B analyzing a total of 5-6 mice/group. (elifesciences.org)
  • D ) Muzzle-infiltrating cells were isolated from indicated mice, stimulated in vitro with PdBu/ionomycin, and analyzed for αβ T cell subset-specific production of IL-17A and IL-22 and for CD4 + T cell production of IL-4, and IL-13. (elifesciences.org)
  • Surprisingly, we previously found that mice deficient in iNKT cells developed spontaneous CD8 + T cells responses partially effective at inhibiting metastases in mice bearing the 4T1 mammary carcinoma, and showed a markedly improved response to treatment with local radiotherapy and anti-CTLA-4 antibody compared to wild type (WT) mice. (biomedcentral.com)
  • To determine if the improved response to treatment in the absence of iNKT cells was independent from the immunotherapy employed, 4T1-tumor bearing WT and iNKT −/− mice were treated with local radiotherapy in combination with antibody-mediated CD137 co-stimulation. (biomedcentral.com)
  • Consistently, priming of T cells to a tumor-specific CD8 T cell epitope in mice treated with radiotherapy and anti-CTLA-4 or anti-CD137 was markedly enhanced in iNKT −/− compared to WT mice. (biomedcentral.com)
  • A distinct TCRβ hi CD4 + T cells subset after anastomosis was 10-20-fold greater than in control mice. (biomedcentral.com)
  • Translational Candidate stem cell-based off-the-shelf CAR-iNKT cells Area of Impact multiple myeloma (MM) Mechanism of Action The proposed therapeutic candidate can directly kill MM tumor cells. (ca.gov)
  • His demonstration that iNKT cells enhance both antigen-specific antibody and T-cell responses has had a major influence on the development of new vaccines and has opened up new therapeutic strategies to enhance immune responses against cancer and infectious pathogens. (aacrjournals.org)
  • Impact Providing the immediate cell therapeutic candidate for clinical trial of diabetic patients. (ca.gov)
  • Research Objective The expected outcome is a therapeutic candidate, allogeneic HSC-engineered HLA-I/II-negative human iNKT cells, that can potentially be used as an off-the-shelf cellular therapy for treating cancer. (ca.gov)
  • 5. MiNK's FAP-CAR-iNKT therapeutic candidate, MiNK-215, demonstrates robust efficacy in non small cell lung cancer (NSCLC) preclinical models, promoting curative responses, eliminating tumor burden in the lungs, and enhancing tumor specific CD8+ T cell infiltration through tumor stroma. (advfn.com)
  • 6. MiNK-413 is a differentiated allogeneic IL-15-armored-BCMA-CAR-iNKT therapeutic candidate, a next generation approach designed to overcome the limitations of current autologous cell therapies. (advfn.com)
  • This dual antitumor function was further enhanced when the iNKT cell agonist α-galactosyl ceramide (α-GalCer) was administered as a therapeutic booster through a platform that ensured controlled delivery at the tumor site, named multistage vector (MSV). (unimib.it)
  • Van Kaer and Wu (2018) have published a review of the therapeutic potential of iNKT cells in autoimmune conditions [ 6 ] and the application of unconventional T cells in immuno-oncology is reviewed by Godfrey et al . (guidetomalariapharmacology.org)
  • Nonetheless, in addition of source of protein antigens, commensal bacteria are a source of lipids capable to activate the lipid-reactive cells named natural killer T (NKT) cells (8,9). (europa.eu)
  • Adipocytes can directly activate CD4 + T cells through antigen:MHCII complex in a contact-dependent manner. (frontiersin.org)
  • Portage's small molecule invariant natural killer T cell (iNKT) engagers may be able to activate the immune response in these patients to effectively identify and target the tumor. (portagebiotech.com)
  • The group studies if cellular stress alters b cells lipid content generating lipid antigens that activate iNKT cells. (uab.cat)
  • The bidirectional activation of iNKT cells and APCs promotes the activation of NK-cell and tumor-specific T-cell responses, thereby mediating tumor-cell killing indirectly. (aacrjournals.org)
  • Her laboratory combines in vitro approaches with live animal modeling to map the regulatory circuits that specify immune cell fate and function and coordinate protective anti-tumor immune responses. (msu.edu)
  • This further supports the hypothesis that there are different trafficking requirements for the development of murine and human iNKT cells, and a functional lysosomal/late-endosomal compartment is not required for human iNKT-cell development. (ox.ac.uk)
  • Yet, if and how the tissue environment shapes the antigen specificity of iNKT cells remains unknown. (elifesciences.org)
  • He showed the proteasome-dependent processing of defined melanoma antigenic proteins into epitopes for antitumor T cells and thus the direct role of immunoproteasomes in cross-presentation of exogenous proteins. (aacrjournals.org)
  • Invariant natural killer T (iNKT) cells possess potent antitumor effects after activation with a specific glycolipid antigen, α-galactosylceramide (αGalCer). (elsevierpure.com)
  • Despite increasing data during the last decades, how commensal lipids are handled by immune cells, the contribution of different APCs to lipid presentation, and their effects on mucosal NKT cells remain poorly understood. (europa.eu)
  • 0.05), suggesting the selective elimination of DCs cross-presenting tumor-associated antigens by iNKT cells. (biomedcentral.com)
  • Research Objective Development of hESC-derived pancreatic beta cells that are protected from allogeneic and autoimmune attack into a cell therapy for type 1 diabetes (T1D) Impact Cell therapy of T1D is challenged by immune rejection. (ca.gov)
  • Insulin-specific autoreactive CD8+ and CD4+ T cells are key at driving the autoimmune response in Type 1 Diabetes. (uab.cat)
  • Analysis of the role of the autoimmune regulator (AIRE) in antigen expression, processing and presentation. (uab.cat)
  • We will also examine the effect of adjuvant combination on class I and class II presentation of co-administered protein antigens. (grantome.com)
  • This interaction results in iNKT activation and cytokine production (IFN gamma, IL-4, IL-13), which takes important part in immune regulation and host response to pathogens and cancer(support of both Th1 and Th2 way), although iNKT cells represent less than 1% of total peripheral T cells. (exbio.cz)
  • agenT-797 restores the cytotoxic capacity, activation, and cytokine production of partially exhausted T cells. (advfn.com)
  • Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells. (ox.ac.uk)
  • Recent studies have highlighted a variety of classes of endogenous and pathogen-derived lipid antigens that can trigger iNKT cell activation under sterile and nonsterile conditions. (ox.ac.uk)
  • These results define a previously unidentified mechanism that controls iNKT cell activation during sterile inflammation. (ox.ac.uk)
  • IEC TLR4 activation and signaling is required for mucosal healing, leading to inflammatory factor release that recruits immune cells to limit bacteria invasion. (biomedcentral.com)
  • Immunometabolic Activation of Invariant Natural Killer T Cells. (ox.ac.uk)
  • In this review, we discuss the contribution of iNKT cell activation to immunometabolic disease, metabolic programming of lipid antigen presentation, and immunometabolic activation of iNKT cells. (ox.ac.uk)
  • Vyth-Dreese FA, Sein J, van de Kasteele W, Dellemijn TA, van den Bogaard C, Nooijen WJ, de Gast GC, Haanen JB, Bex A: Lack of anti-tumour reactivity despite enhanced numbers of circulating natural killer T cells in two patients with metastatic renal cell carcinoma. (exbio.cz)
  • Krovi SH, Gapin L: Invariant natural killer T cell subsets - more than just developmental intermediates. (exbio.cz)
  • Natural killer (NK) cells were identified in the blood and lymphoid organs of humans and experimental animals as cells capable of killing tumors, virus-infected cells, and, in some instances, normal cells, in the absence of previous deliberate or known sensitization. (mhmedical.com)
  • Invariant natural killer T (iNKT) cells are lipid-reactive T cells with profound immunomodulatory potential. (ox.ac.uk)
  • Invariant natural killer T cells are not affected by lysosomal storage in patients with Niemann-Pick disease type C. (ox.ac.uk)
  • While defects in lipid antigen presentation hN-CoR and in invariant Natural Killer T (iNKT) cell response were detected in several mouse models of lysosomal storage diseases (LSD), the impact of lysosomal engorgement in human lipid antigen presentation is poorly characterized. (clinical-research-informatics.com)
  • Her research focuses on how invariant natural killer T (iNKT) cells recognize and respond to malignant or infected cells. (msu.edu)
  • Lately, it has been described a novel function for ILCs as antigen presenting cells (APCs) through MHC-II-dependent presentation of commensal-derived antigens (3-7). (europa.eu)
  • However, the context and mechanisms that drive the presentation of self-lipid antigens in sterile inflammation remain unclear. (ox.ac.uk)
  • Second, we discuss the effects of cellular metabolism on lipid antigen processing and presentation to iNKT cells. (ox.ac.uk)
  • 2005 This possibility was supported by a recent study using lineage-specific conditional deletion of gene expression which identified presentation by different types of antigen-presenting cells (APCs) as a major factor underlying the cytokine biasing properties of different αGC variants (Bai et?al. (biotech-angels.com)
  • Data_Sheet_1.pdf (513K) GUID:?514B8128-1B6A-4BCF-ADFD-8945AF1CB772 Supplementary Physique 3: Statistical analysis of CD1b-restricted lipid antigen presentation by Mo-DCs. (clinical-research-informatics.com)
  • These preclinical results support the combination of tumor-redirected TCR-iNKT cells and local α-GalCer boosting as a potential therapy for patients with cancer. (unimib.it)
  • Preclinical data for PORT-3 was published in the journal Frontiers in Immunology in February 2021 and demonstrated good tolerability and a strong cancer-specific B and T-cell response. (portagebiotech.com)
  • A smaller NKT cell subset utilizes a more diverse set of TCR αβ chains and is referred to as type II or non-invariant NKT cells [ 7 ]. (biomedcentral.com)
  • The synthesis and processing of glycolipids and other potential endogenous lipid antigens depends on metabolic demand and may steer iNKT cells toward adopting a Th1 or Th2 signature. (ox.ac.uk)
  • TCR-iNKT cells achieved robust cancer control by simultaneously modulating intratumoral suppressive myeloid populations and killing malignant cells. (unimib.it)
  • GC adjuvant stimulates semi-invariant TCR-expressing Type I NKT cells (iNKT) and results in a mixed Th1/Th2 response. (grantome.com)
  • Upon in vivo transfer, TCR-engineered iNKT (TCR-iNKT) cells showed the highest efficacy in restraining the progression of multiple tumors that expressed the cognate antigen compared with nontransduced iNKT cells or CD8+ T cells engineered with the same TCR. (unimib.it)
  • Here we describe a novel mechanism of tumor immune escape mediated by iNKT cells that limit priming of anti-tumor T cells by controlling DC in tumors and draining lymph nodes. (biomedcentral.com)
  • Portage's iNKT engager, IMM60, can also be co-delivered with antigen-specific vaccines to target tumors that express a specific antigen, such as NY-ESO-1. (portagebiotech.com)
  • In T1D patients NKT cells seem to lose their regulatory capacity which can be associated to a poor IL13 production at disease onset. (uab.cat)
  • The regulatory deficiency of NKT cells in T1D patients can be related to a differentiated gene expression pattern compared to NKT cells from healthy controls (ongoing research). (uab.cat)
  • We isolated fecal content and small intestinal leukocytes from murine, Roux-en-Y and end-to-end anastomoses, to identify microbiome changes and subsequent alterations in the regulatory and pro-inflammatory immune cells 3 days post-operative. (biomedcentral.com)
  • The mouse monoclonal antibody 6B11 recognizes an extracellular epitope within V alpha 24 J alpha 18 TCR, which is expressed by invariant NK T cells (iNKT). (exbio.cz)
  • As a result of the progress of the project, it was found that NKT cell-APCs crosstalk is a key mechanism for the regulation of intestinal homeostasis. (europa.eu)
  • First, we introduce adipocytes as APCs to participate in T cell-mediated adaptive immune response. (frontiersin.org)
  • Siglec-1 may mediate both sialic-acid-independent and sialic-acid-dependent connections with cells from the disease fighting capability [6]. (techblessing.com)
  • It is known that interactions between immune system and commensal bacteria are complex and involved several immune cell types. (europa.eu)
  • Healing is a concerted effort between intestinal epithelial cells (IECs), immune cells, and commensal bacteria. (biomedcentral.com)
  • As a consequence of treatments, the most frequent mechanism of cell death is apoptosis, followed by autophagy. (frontiersin.org)
  • Translational Candidate s15.BsAb.BCMA-CAR NK cells derived from CD34(+) umbilical cord blood hematopoietic stem cells Area of Impact patients with multiple myeloma Mechanism of Action s15.BsAb.BCMA-CAR NK cells are umbilical cord blood-derived CD34+ hematopoietic stem cells that are engineered to include two components of the BCMA-CAR and the anti-NKG2D-anti-GPRC5D BsAb. (ca.gov)