Background: Dendritic cells (DCs) are professional antigen presenting cells that have an important role in the initiation of immune response. The use of maturation factors in dendritic cell differentiation provides a promising approach in immunotherapy. Objective: In this study, we compared tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG oligonucleotides in inducing dendritic cell maturation. Methods: We generated immature dendritic cells with GM-CSF in combination with IL-4 from peripheral blood mononuclear adherent cells and used tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG for the induction of dendritic cell maturation. CD83 maturation marker on the dendritic cells was analyzed by flowcytometry after 7 days. In addition, mixed leukocyte reaction between dendritic cells and T cells was performed by MTT proliferation assay. Results: Flow cytometry results demonstrated a comparable high level of CD83 expression on the mature dendritic cells
Objective: Sjögrens syndrome (SS) is a lymphoproliferative autoimmune disease, characterized by dryness of the mouth and eyes. Dendritic cells (DC) are potent antigen-presenting cells and crucial for initiating and maintaining primary immune responses. Here, we quantified interferon producing plasmacytoid DC (pDC) and two myeloid DC subsets (mDC1 and mDC2) in human peripheral blood from primary SS (pSS) patients and healthy controls in order to investigate whether alterations among DC subsets play a potential role in the disease. Method: Blood samples from 31 pSS patients and 28 gender- and age-matched healthy controls were analyzed by flow cytometry using the Miltenyi Blood DC Enumeration kit. The presence of pDC in salivary glands (SG) from pSS patients was analyzed by immunohistochemistry. Results: Patients with pSS had significantly less pDC and mDC2 in peripheral blood compared to healthy controls. Moreover, pDC are present in SG from patients with pSS. Conclusion: Alterations among DC ...
Dendritic cell-based immunotherapy employs the patients immune system to fight neoplastic lesions spread over the entire body. This makes it an important therapy option for patients suffering from metastatic melanoma, which is often resistant to chemotherapy. However, conventional cellular vaccination approaches, based on monocyte-derived dendritic cells, only achieved modest response rates despite continued optimization of various vaccination parameters. In addition, the generation of monocyte-derived dendritic cells requires extensive ex vivo culture conceivably hampering the immunogenicity of the vaccine. Recent studies, thus, focused on vaccines that make use of primary dendritic cells. Though rare in the blood, these naturally circulating dendritic cells can be readily isolated and activated thereby circumventing lengthy ex vivo culture periods. The first clinical trials not only showed increased survival rates but also the induction of diversified anticancer immune responses. Upcoming treatment
Background: Dendritic cells (DCs) are professional antigen-presenting cells able to induce immunity or tolerance. The interactions of immature DCs with naive T lymphocytes induce peripheral tolerance through mechanisms that include anergy or deletion of lymphocytes or the generation of regulatory T cells. Because of the central role of DCs in the immune response, they are potential targets for the induction of experimental tolerance. Thus, the generation of immature (tolerogenic) DCs able to capture and present alloantigens to T cells represents an important aim in our efforts to achieve better transplant acceptance. Methods: In this work, we generated immature DCs by using vitamin D 3 (VD3) during the process of DC differentiation. Results: The VD3DCs showed an immature phenotype characterized by a low expression of major histocompatibility complex antigens of class II, CD86, and CD80 molecules and the secretion of a tolerogenic cytokine pattern. Furthermore, we showed that VD3DCs ...
Dendritic Cell Vaccines have been around for over 20 years but early results suggested they had an effect in only 12% of brain cancer patients; but now in a new 4 country clinical trial, Dendritic Cell Vaccine (DCVax -L) seems to give some patients over 7 years of extra survival, fulfilling the early promise of this form of immunotherapy for brain tumours.. Using Temozolomide with Dendritic Cell Vaccine ((DCVax ® -L). For patients with GBM, standard treatment involves surgery, radiotherapy and temozolomide. Here, the researchers announced results of their Phase III trial where an autologous tumour-lysate-pulsed Dendritic Cell Vaccine ((DCVax ® -L) was added to the standard programme.. In this study patients after surgery received either Temozolomide plus the vaccine, or Temozolomide plus a placebo.. However, where recurrence occurred all patients were allowed to have the Dendritic Cell vaccine.. The Intention to Treat (ITT) mean Overall Survival time was shown to be 23.3 months from ...
Dendritic cells (DCs) are potent antigen-presenting cells endowed with the unique ability to initiate adaptive immune responses upon inflammation. Inflammatory processes are often associated with an increased production of serotonin, which operates by activating specific receptors. However, the functional role of serotonin receptors in regulation of DC functions is poorly understood. Here we demonstrate that expression of serotonin receptor 5-HT7 (5-HT7R) as well as its down-stream effector Cdc42 is upregulated in DCs upon maturation. While DC maturation was independent of 5-HT7R, receptor stimulation affected DC morphology via Cdc42-mediated signaling. In addition, basal activity of 5-HT7R was required for the proper expression of the chemokine receptor CCR7, which is a key factor to control DC migration. Consistently, we observed that 5-HT7R enhances chemotactic motility of DCs in vitro by modulating their directionality and migration velocity. Accordingly, migration of DCs in murine colon ...
Dendritic cells (DCs) are professional antigen-presenting cells of the immune system with the ability to induce and control T and B cells responses. Monocytes have been used as precursors to generate DC vaccines ex vivo. Monocyte-derived DCs have been used as vaccines in clinical trials to treat cancer and infectious disease by eliciting potent T cell responses. Infection with Human Immunodeficiency Virus (HIV) almost invariably leads to a chronic disease. Eventually the destruction of the immune system culminates into Acquired Immune Deficiency Syndrome (AIDS). Since the advent of Highly Active Antiretroviral Therapy (HAART), HIV patients have been able to control viral levels. However, with prolonged use of treatment, these patients experience serious adverse effects such as liver and mitochondrial toxicity that can potentially become fatal. Long-Term Non-Progressors (LTNP) are a unique subpopulation of HIV patients that are able to control their viral load without HAART. Studies revealed ...
Dendritic cells (DCs) are potent antigen-presenting cells that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, we injected 9 healthy subjects subcutaneously with a control injection of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by DCs pulsed with keyhole limpet hemocyanin (KLH), HLA-A*0201-positive restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more subjects received these antigens without DCs. Injection of unpulsed DCs, or antigens alone, failed to immunize. Priming of CD4(+) T cells to KLH was observed in all 9 subjects injected with KLH-pulsed DCs, and boosting of TT-specific T-cell immunity was seen in 5 of 6 subjects injected with TT-pulsed DCs. Injection of antigen-pulsed DCs led to a severalfold increase in freshly isolated MP-specific, IFN-gamma-secreting CD8(+) T cells in all 6 HLA-A*0201-positive subjects, as early as 7 days after injection. When T cells were boosted in culture, there was an increase in
Cell surface markers of mouse thymic dendritic cells have been studied by flow cytometry after isolation by collagenase digestion, separation of the low-density cell fraction and differential adherence. The dendritic cell preparation had a purity of , 90%, the contaminating population being essentially composed of thymocytes, macrophages constituting ,1%. Dendritic cells displayed high forward and low-intermediate side angle scatter, and expressed high levels of major histocompatibility complex (MHC) class I and class II molecules, the heat-stable antigen (HSA), the adhesion molecules Pgp-1 (CD44), LFA-1, ICAM-1 and low levels of Mac-1 and the leukocyte common antigen CD45. Thymic dendritic cells are negative for the stem cell antigen-2 (Sca-2), the B cell-specific form of CD45 (B220), the mouse macrophage markers Fc receptor and F4/80, and the granulocyte marker Gr-1. However, although they do not express the T cell markers Thy-1, CD2, CD3, CD4 and CD5, 20%-30% of dendritic cells are positive ...
Myeloid dendritic cells (DCs) are professional antigen-presenting cells critical for the orchestration of immunity and maintenance of self-tolerance. DC development and functions are tightly regulated by
TY - JOUR. T1 - Functional redundancy between thymic CD8α+and Sirpα+ conventional dendritic cells in presentation of blood-derived lysozyme by MHC class II proteins. AU - Atibalentja, Danielle F.. AU - Murphy, Kenneth M.. AU - Unanue, Emil R.. PY - 2011/2/1. Y1 - 2011/2/1. N2 - We evaluated the presentation of blood-derived protein Ags by APCs in the thymus. Two conventional dendritic cells (cDCs), the CD8α +Sirpa-CD11chi (CD8α+ cDC) and the CD8α-Sirpα+CD11chi (Sirpa + cDC), were previously identified as presenting MHC class II bound peptides from hen egg white lysozyme (HEL) injected intravenously. All thymic APCs acquired the injected HEL, with the plasmacytoid dendritic cell being the best, followed by the Sirpα+ cDC and the CD8α+ cDC. Both cDCs induced to similar extent negative selection and regulatory T cells in HEL TCR transgenic mice, indicating a redundant role of the two cDC subsets in the presentation of blood-borne HEL. Immature dendritic cells or plasmacytoid dendritic cells ...
1. ShortmanK. LiuYJ. 2002. Mouse and human dendritic cell subtypes.. Nat Rev Immunol. 2. 151. 161. 2. AlmeidaM. CorderoM. AlmeidaJ. OrfaoA. 2005. Different subsets of peripheral blood dendritic cells show distinct phenotypic and functional abnormalities in HIV-1 infection.. AIDS. 19. 261. 271. 3. BarronMA. BlyveisN. PalmerBE. MaWhinneyS. WilsonCC. 2003. Influence of plasma viremia on defects in number and immunophenotype of blood dendritic cell subsets in human immunodeficiency virus 1-infected individuals.. J Infect Dis. 187. 26. 37. 4. DonaghyH. PozniakA. GazzardB. QaziN. GilmourJ. 2001. Loss of blood CD11c(+) myeloid and CD11c(−) plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load.. Blood. 98. 2574. 2576. 5. GrassiF. HosmalinA. McIlroyD. CalvezV. DebreP. 1999. Depletion in blood CD11c-positive dendritic cells from HIV-infected patients.. AIDS. 13. 759. 766. 6. PacanowskiJ. KahiS. BailletM. LebonP. DeveauC. 2001. Reduced blood CD123+ (lymphoid) ...
1. Banchereau J, Steinman R.M. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245-52 2. Zitvogel L. Dendritic and natural killer cells cooperate in the control/switch of innate immunity. J Exp Med. 2002;195(3):F9-14 3. Banchereau J. et al. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767-811 4. Lanzavecchia A, Sallusto F. Regulation of T cell immunity by dendritic cells. Cell. 2001;106(3):263-6 5. Garg S. et al. Genetic tagging shows increased frequency and longevity of antigen-presenting, skin-derived dendritic cells in vivo. Nat Immunol. 2003;4(9):907-12 6. Mellman I, Steinman R.M. Dendritic cells: specialized and regulated antigen processing machines. Cell. 2001;106(3):255-8 7. Zhang Z. et al. Differential restoration of myeloid and plasmacytoid dendritic cells in HIV-1-infected children after treatment with highly active antiretroviral therapy. Immunol J. 2006;176(9):5644-51 8. Allan R.S. et al. Epidermal viral immunity induced by CD8alpha+ dendritic cells ...
TY - JOUR. T1 - Human peripheral blood dendritic cells and monocyte subsets display similar chemokine receptor expression profiles with differential migratory responses. AU - Cravens, P. D.. AU - Hayashida, K.. AU - Davis, L. S.. AU - Nanki, T.. AU - Lipsky, P. E.. PY - 2007/6. Y1 - 2007/6. N2 - Human antigen presenting cells (APC) found in peripheral blood are considered to be precursors that have been released from the bone marrow and are in transit to the peripheral tissues. These APC populations include myeloid dendritic cells (mDC), plasmacytoid DC (pDC) and monocytes (Mo). To assign specialized functional roles and stages of development for APCs, CD33 expressing APC subsets were examined for their capacity to respond to chemokines. Three major CD33+ subsets including CD33brightCD14 bright Mo, CD33brightCD14- CD11c+ mDC and CD33dimCD14- pDC were present. Dendritic cells subsets and Mo expressed low levels of CC and CXC receptors, but distinctive chemokine receptor expression profiles were ...
CYTIP (cytohesin interacting protein) is an intracellular molecule induced in dendritic cells during maturation. CYTIP modulates the binding intensity of the adhesion molecule LFA-1. If dendritic cells are silenced for CYTIP they keep longer contacts with T-cells resulting in a lower T cell stimulation. We identified Suppressor of cytokine signaling-1 (SOCS-1) as a binding partner for CYTIP in human monocyte derived dendritic cells. In Western blot analyses we found that CYTIP expression is down regulated at later time points, starting at about 72 hours after induction of maturation. To investigate a possible role for SOCS-1 in taking CYTIP to the degradation machinery of the cell we measured endogenous CYTIP protein levels in mature dendritic cells transfected with SOCS-1 encoding plasmid in quantitative Western blot analyses. We observed lower amounts of endogenous CYTIP in mature dendritic cells transfected with SOCS-1 encoding plasmid compared with untransfected dendritic cells. Experiments with the
TY - JOUR. T1 - Morphine inhibits murine dendritic cell IL-23 production by modulating toll-like receptor 2 and Nod2 signaling. AU - Wang, Jinghua. AU - Ma, Jing. AU - Charboneau, Rick. AU - Barke, Roderick. AU - Roy, Sabita. PY - 2011/3/25. Y1 - 2011/3/25. N2 - IL-23, produced by dendritic cells (DCs) and macrophages, plays a critical role in innate immunity against bacterial infection. Our previous studies show that morphine disrupts the IL-23/IL-17 mediated pulmonary mucosal host defense and increases susceptibility to Streptococcus pneumoniae lung infection. To determine the mechanism by which morphine modulates IL-23 production, mouse bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) were treated with morphine, and infected with S. pneumoniae or stimulated with Toll-like receptor (TLR) and Nod2 ligands. We found that a significant increase in IL-23 protein production was observed in S. pneumoniae, TLR2 ligand lipoteichoic acid (LTA), and TLR4 ligand pneumolysin (PLY) ...
This study is being done to see if the investigators can help the immune system to work against melanoma.. A dendritic cell is another type of white blood cell. It has most, if not all, of the proteins needed to make T cells work to destroy cancer cells. However, dendritic cells do not normally have the cancer proteins on their surface. The challenge then is to combine the antigens with dendritic cells to make a vaccine. The investigators think that the bodys T cells might then react against the tumor and help destroy it.. This study will see if altered dendritic cells will make T cells work against tumor cells. The dendritic cells will be made in a lab and will carry the antigens. These cells then will be injected under the skin.. In this study, the investigators are trying to help the body make a stronger immune response against the cancer. The patient will get the same kind of dendritic cell vaccine used in the earlier study, but with one major difference. The dendritic cells will contain ...
Results In their resting state the monocyte derived dendritic cells expressed MHC class II, but very low levels of co-stimulatory molecules CD80, CD83 and CD86. Upon culture with H. pylori, the cells expressed significantly higher levels of these co-stimulatory molecules, demonstrating maturation (,25 fold increase in percentage of positive events for CD80, CD83, CD86 on flow cytometry; p,0.01). There were no differences between the responses to wild type and dupA knockout mutant strains, or following stimulation with lipopolysaccharide (LPS). The H. pylori-matured dendritic cells secreted high levels of IL-12p40, IL-12p70, IL-10 and IL-23. The concentrations induced by the dupA+ strains were significantly higher than those induced by the dupA mutants (1.5 fold increase in IL-12p40 production, p,0.05; 1.4 fold increase in IL-12p70, p,0.05).. ...
Chang S-Y, Song J-H, Guleng B, Cotoner CA, Arihiro S, Zhao Y, Chiang H-S, OKeeffe M, Liao G, Karp CL, et al. Circulatory antigen processing by mucosal dendritic cells controls CD8(+) T cell activation. Immunity. 2013;38 (1) :153-65.
Dendritic cells, particularly those residing in the spleen, are thought to orchestrate acquired immunity to malaria, but it is not known how the splenic dendritic cell population responds to malaria infection and how this response compares with the responses of other antigen-presenting cells. We investigated this question for Plasmodium chabaudi AS infection in C57BL/6 mice. We found that dendritic cells, defined here by the CD11c marker, migrated from the marginal zone of the spleen into the CD4(+) T-cell area within 5 days after parasites entered the bloodstream. This contrasted with the results observed for the macrophage and B-cell populations, which expanded greatly but did not show any comparable migration. Over the same time period dendritic cells showed upregulation of CD40, CD54, and CD86 costimulatory molecules that are required for successful T-cell activation. In dendritic cells, the peak intracellular gamma interferon expression (as shown by fluorescence-activated cell sorting) was on day 5
Tumor-infiltrating dendritic cell subsets of progressive or regressive tumors induce suppressive or protective immune responses. - Yongqing Liu, Xuguang Bi, Shulin Xu, Jim Xiang
Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here, we combine two high-dimensional technologies-s …
Dendritic cells represent important components of the innate and adaptive immune responses. Human dendritic cells can be divided into two major subsets: myeloid and plasmacytoid (lymphoid) dendritic cells. The unique function of the dendritic cells is to capture antigens, present and to activate the antigenic peptides to the T lymphocytes. Dendritic cells go through a maturation process both in vitro and in vivo. By the use of pathogenrecognition- receptors the immature dendritic cells sense diverse pathogens or their various components, or cellular factors produced by the infected neighboring non-dendritic cells, and maturation signals are transduced for the dendritic cells. The heterogeneity of the pathogen-recognition-receptors and the microbial stimuli initiate a broad range of interactions between dendritic cells and infectious agents. Dendritic cells infected with certain viruses produce only a few infectious particles, but express and present viral antigens to T lymphocytes and immune ...
Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a critical role in the induction of antitumor immunity. Therefore, various strategies have been developed to deliver tumor-associated antigens (TAAs) to DCs as cancer vaccines. The fusion of DCs and whole tumor cells to generate DC-tumor fusion cells (DC-tumor FCs) is an alternative strategy to treat cancer patients. The cell fusion method allows DCs to be exposed to the broad array of TAAs originally expressed by whole tumor cells. DCs then process TAAs endogenously and present them through major histocompatibility complex (MHC) class I and II pathways in the context of costimulatory molecules, resulting in simultaneous activation of both CD4+ and CD8+ T cells. DC-tumor FCs require optimized enhanced immunogenicity of both DCs and whole tumor cells. In this context, an effective fusion strategy also needs to produce immunogenic DC-tumor FCs. We discuss the potential ability of DC-tumor FCs and the recent progress in improving
4717 A lipoteichoic acid-related molecule OK-PSA is an active component of OK-432, a Streptococcus-derived anti-cancer immunotherapeutic agent. We have reported that OK-PSA has an ability to mature dendritic cells (DCs) via Toll-like receptor (TLR) 4 signaling. DCs are potent antigen-presenting cells which promote immune responses against tumor cells. It is important to mature DCs capturing tumor antigen to enhance their anti-tumor activity. TLR4 plays a significant role in recognition of bacterial components as well as in activation of innate and acquired immunity. In the current study, we investigated the role of TLR4 in the anti-tumor effect of intratumoral administration of bone marrow-derived DCs followed by OK-PSA against established tumors in mice. C57BL/6 mice which are expressing wild-type TLR4, and C57BL/6-derived TLR4-knockout (TLR4-/-) mice were used for the present experiments. We first examined the effect of OK-PSA in the in vitro maturation of DCs. OK-PSA increased the expression ...
A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells are required to explain how this remarkable system is energized and directed. I frame this article in terms of the major decisions that my colleagues and I have made in dendritic cell science and some of the guiding themes at the time the decisions were made. As a result of progress worldwide, there is now evidence of a central role for dendritic cells in initiating antigen-specific immunity and tolerance. The in vivo distribution and development of a previously unrecognized white cell lineage is better understood, as is the importance of dendritic cell maturation to link innate and adaptive immunity in response to many stimuli. Our current focus is on antigen uptake receptors on dendritic cells. These receptors enable experiments involving selective targeting of
Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by an aberrant immune response to microbial components of the gastrointestinal tract. Plasmacytoid dendritic cells (pDCs) are innate immune cells specialized in the production of type I interferons and were recently implicated in the pathogenesis of autoimmune disorders such as lupus and scleroderma. While pDCs were shown to infiltrate intestinal mucosa of IBD patients and proposed to participate in intestinal inflammation, their net contribution to the disease remains unclear. We addressed this question by targeting the pDC-specific transcription factor TCF4 (E2-2) in experimental IBD caused by deficiency of Wiskott-Aldrich syndrome protein (WASP) or of interleukin-10 (IL-10). Monoallelic Tcf4 deletion, which was previously shown to abrogate experimental lupus, did not affect autoimmunity manifestations or colitis in WASP-deficient animals. Furthermore, conditional biallelic Tcf4 targeting resulted in a near-complete pDC
Dendritic cells are the messengers of the immune system, transporting antigens from sites of inflammation to the lymph organs that serve as central hubs for immune activation. Ufer et al. have identified a neuronal plasticity molecule-activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1)-that is expressed in migratory dendritic cells in the skin. Arc/Arg3.1 regulates cytoskeletal changes in dendritic cells, accelerating migration in response to inflammation. Moreover, Arc/Arg3.1 was required for inducing T cell responses in two different disease models-experimental autoimmune encephalitis and allergic contact dermatitis. Targeting Arc/Arg3.1 may therefore be a therapeutic strategy to modify dendritic cell immunotherapy. ...
According to Daniel Hawiger, dendritic cells "are the music directors, telling other lymphocytes such as T cells what to do and how to do it." Hawiger is the senior author of a study recently published in the journal Immunity. The study (Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells) helps to understand how dendritic cells direct T lymphocytes to learn tolerance for the bodys own antigens. "T cells are the immune systems fighters," Hawiger said. "Dendritic cells help train T cells to distinguish between self and non-self.". Dendritic cells were first described by Ralph Steinman in the 1970s and, since the 1980s, it has been known that one of the major functions of dendritic cells is antigen presentation-the display of peptides derived from viral and cancer antigens to T lymphocytes. Following recognition of peptides, T lymphocytes become activated and initiate a complex set of events. These events require the ...
TY - JOUR. T1 - Decellularized lymph node scaffolding as a carrier for dendritic cells to induce anti-tumor immunity. AU - Lin, Hung Jun. AU - Wang, Weu. AU - Huang, Yi You. AU - Liao, Wei Tsen. AU - Lin, Ting Yu. AU - Lin, Shyr Yi. AU - Liu, Der Zen. PY - 2019/11. Y1 - 2019/11. N2 - In recent decades, the decellularized extracellular matrix (ECM) has shown potential as a promising scaffold for tissue regeneration. In this study, an organic acid decellularized lymph node (dLN) was developed as a carrier for dendritic cells (DCs) to induce antitumor immunity. The dLNs were prepared by formic acid, acetic acid, or citric acid treatment. The results showed highly efficient removal of cell debris from the lymph node and great preservation of ECM architecture and biomolecules. In addition, bone marrow dendritic cells (BMDCs) grown preferably inside the dLN displayed the maturation markers CD80, CD86, and major histocompatibility complex (MHC)-II, and they produced high levels of interleukin (IL)-1β, ...
TY - JOUR. T1 - Stromal fibroblasts support dendritic cells to maintain IL-23/Th17 responses after exposure to ionizing radiation. AU - Malecka, Anna. AU - Wang, Qunwei. AU - Shah, Sabaria. AU - Sutavani, Ruhcha V.. AU - Spendlove, Ian. AU - Ramage, Judith M.. AU - Greensmith, Julie. AU - Franks, Hester A.. AU - Gough, Michael J.. AU - Saalbach, Anja. AU - Patel, Poulam M.. AU - Jackson, Andrew M.. PY - 2016/8/1. Y1 - 2016/8/1. N2 - Dendritic cell function is modulated by stromal cells, including fibroblasts. Although poorly understood, the signals delivered through this crosstalk substantially alter dendritic cell biology. This is well illustrated with release of TNF-α/IL-1β from activated dendritic cells, promoting PGE2 secretion from stromal fibroblasts. This instructs dendritic cells to up-regulate IL-23, a key Th17-polarizing cytokine. We previously showed that ionizing radiation inhibited IL-23 production by human dendritic cells in vitro. In the present study, we investigated the ...
Supplementary Material for: Cross-Talk between Human Dendritic Cell Subsets Influences Expression of RNA Sensors and Inhibits Picornavirus Infection
Insufficient elimination of the hepatitis C virus (HCV) during acute infection results in chronic disease in the majority of patients due to weak virus-specific immune responses. Dendritic cells (DC) play a central role in recognition of HCV and in induction of innate and adaptive immune responses. In this study, we evaluated the frequency and functions of plasmacytoid dendritic cells (PDC) and myeloid dendritic cells (MDC) in patients with chronic HCV infection. We found that both the numbers and IFNalpha production capacity of blood PDC were significantly reduced in patients with chronic HCV infection compared to normal controls. While the frequency of MDC was not affected in chronic HCV, the allostimulatory capacity of monocyte-derived MDC was significantly decreased compared to normals. Lipopolysaccharide (LPS)-induced maturation improved the allostimulatory capacity of HCV infected patients MDC that still remained significantly lower compared to normal controls. Our experiments revealed that MDC
Alpha-fetoprotein (AFP) is a tumor-associated glycoprotein that functions in regulation of both ontogenic and oncogenic growth. Recent study showed that AFP can induce apoptosis or impair monocyte-derived dendritic cell (MDDC) function. However, it is still unclear which AFP domain (D-AFP) plays major role in this function. As expected monocytes cultured in the presence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin-4 (IL-4) developed into MDDC. Up-regulation of HLA-DR and CD11c as well as loss of CD14 molecules could be observed. Full length AFP (FL-AFP), domain 2 AFP (D2-AFP) and D3-AFP, but not D1-AFP, significantly inhibited the expression of HLA-DRhigh/CD11chigh and CD80+/CD86high molecules. In contrast, CD83 expression was substantially down-regulated in all samples. Expression of CD40 was significantly suppressed by FL-AFP but not by any D-AFPs. Finally, both FL-AFP and D-AFP impaired the MDDC ability to secrete IL-12 (p70). D2- and D3- but not D1-AFP extensively
Alpha-fetoprotein (AFP) is a tumor-associated glycoprotein that functions in regulation of both ontogenic and oncogenic growth. Recent study showed that AFP can induce apoptosis or impair monocyte-derived dendritic cell (MDDC) function. However, it is still unclear which AFP domain (D-AFP) plays major role in this function. As expected monocytes cultured in the presence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin-4 (IL-4) developed into MDDC. Up-regulation of HLA-DR and CD11c as well as loss of CD14 molecules could be observed. Full length AFP (FL-AFP), domain 2 AFP (D2-AFP) and D3-AFP, but not D1-AFP, significantly inhibited the expression of HLA-DRhigh/CD11chigh and CD80+/CD86high molecules. In contrast, CD83 expression was substantially down-regulated in all samples. Expression of CD40 was significantly suppressed by FL-AFP but not by any D-AFPs. Finally, both FL-AFP and D-AFP impaired the MDDC ability to secrete IL-12 (p70). D2- and D3- but not D1-AFP extensively
Dendritic cells (DCs) play important roles in immune recognition of invading pathogens during infections. They bridge the two branches of innate and adaptive immunity and are thought to be unique in their capacity to prime naive T cell responses. DCs act as sentinels, responding to evolutionary-conserved microbial structures as indicators of infection, using pattern recognition receptors. TLRs are the best characterized group of pattern recognition receptors that recognize pathogen-associated molecular patterns such as LPS, peptidoglycans, flagellin, lipoteichoic acid, or unmethylated CpG DNA, and they can stimulate activation of the innate immune system (1, 2). As a result, DCs change their activation state, gaining immunostimulatory capacity hallmarked by reinforced migratory homing to secondary lymphoid tissues, increased Ag processing and presentation, expression of costimulatory molecules, and secretion of proinflammatory cytokines. These activation-associated changes enable DCs to prime ...
While much is understood about dendritic cells and their role in the immune system, the study of these cells is critical to gain a more complete understanding of their function. Dendritic cell isolation from mouse body tissues can be difficult and the number of cells isolated small. This protocol describes the growth of large number of dendritic cells from the culture of mouse
TY - JOUR. T1 - A subset of toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells. AU - Datta, Sandip K.. AU - Redecke, Vanessa. AU - Prilliman, Kiley R.. AU - Takabayashi, Kenji. AU - Corr, Maripat. AU - Tallant, Thomas. AU - DiDonato, Joseph. AU - Dziarski, Roman. AU - Akira, Shizuo. AU - Schoenberger, Stephen P.. AU - Raz, Eyal. PY - 2003/4/15. Y1 - 2003/4/15. N2 - Dendritic cells (DCs) are capable of cross-presenting exogenous Ag to CD8+ CTLs. Detection of microbial products by Toll-like receptors (TLRs) leads to activation of DCs and subsequent orchestration of an adaptive immune response. We hypothesized that microbial TLR ligands could activate DCs to cross-present Ag to CTLs. Using DCs and CTLs in an in vitro cross- presentation system, we show that a subset of microbial TLR ligands, namely ligands of TLR3 (poly(inosinic-cytidylic) acid) and TLR9 (immunostimulatory CpG DNA), induces cross-presentation. In contrast to presentation of Ag to CD4+ T ...
TY - JOUR. T1 - Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid. AU - Feng, Ting. AU - Cong, Yingzi. AU - Qin, Hongwei. AU - Benveniste, Etty N.. AU - Elson, Charles O.. PY - 2010/11/15. Y1 - 2010/11/15. N2 - It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that a subset of bone marrow cells freshly isolated from C57BL/6 mice express the retinoic acid (RA)-synthesizing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1a2) and are capable of providing RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs to express CCR9 and ALDH1a2 and conferred upon them mucosal DC functions, including induction of Foxp3 + regulatory T cells, IgA-secreting B cells, and gut-homing molecules. This response of DCs to RA was dependent on a narrow time window and stringent dose effect. RA promoted bone marrow-derived DC production of bioactive TGF-β by ...
Ectopic expression of transcription factors has been used to reprogram differentiated somatic cells toward pluripotency or to directly reprogram them to other somatic cell lineages. This concept has been explored in the context of regenerative medicine. Here, we set out to generate dendritic cells (DCs) capable of presenting antigens from mouse and human fibroblasts. By screening combinations of 18 transcription factors that are expressed in DCs, we have identified PU.1, IRF8, and BATF3 transcription factors as being sufficient to reprogram both mouse and human fibroblasts to induced DCs (iDCs). iDCs acquire a conventional DC type 1-like transcriptional program, with features of interferon-induced maturation. iDCs secrete inflammatory cytokines and have the ability to engulf, process, and present antigens to T cells. Furthermore, we demonstrate that murine iDCs generated here were able to cross-present antigens to CD8+ T cells. Our reprogramming system should facilitate better understanding of ...
Plasmacytoid DCs (pDCs) comprise one of two major subsets of human DCs. The myeloid subset is characterized by the presence of CD11c, whereas pDCs correspond to a small subset of CD11c-negative circulating blood DCs (1). Human pDCs are CD4+ CD45RA+IL-3Rα+ (CD123) ILT3+ILT1− CD11c− lineage− cells (2). Two additional markers, BDCA-2 and BDCA-4 are expressed on human pDCs in peripheral blood and bone marrow (3).. In response to viral and bacterial stimuli, pDCs can mature and produce large amounts of type I IFNs (IFN-α/β) (4). Type I interferons activate NK cell cytolytic activity, but protect uninfected cells from NK cell-mediated lysis and affect T cell function by inducing Th1 differentiation (5). Moreover, type I interferons promote differentiation, maturation, and immunostimulatory functions of DCs.. Recent findings suggest that pDCs play an important role in the balance of immune responses. Although resting pDCs may induce regulatory responses, their activated counterparts have a ...
Mimicking the immunoregulatory properties of primary dendritic cells in vitro − A rational approach to design a test system ...
The Blood Dendritic Cell Enumeration Kit was developed for easy identification and enumeration of dendritic cells (DCs) and DC subsets in whole blood or PBMCs by flow cytometry. All reagents required for the analysis are included in the kit. Applications of the kit include monitoring of peripheral blood DC frequency and number, for example, after hematopoietic stem cell mobilization3 , or in the course of pathogenic infections, for example by HIV.4 Furthermore, DC numbers were determined in patients with chronic graft versus host disease5 , inflammatory bowel disease6 , psoriatic arthritis and rheumatoid arthritis10 , under long-term immunosuppression8 , lymphoproliferative disease of granular lymphocytes9 , or in patients with hepatocellular carcinoma, in order to analyze the immunosuppressive role of IL-10 on circulating dendritic cells7 . - Latvija
TY - JOUR. T1 - In vivo and in vitro analyses of α-galactosylceramide uptake by conventional dendritic cell subsets using its fluorescence-labeled derivative. AU - Ushida, Maki. AU - Iyoda, Tomonori. AU - Kanamori, Mitsuhiro. AU - Watarai, Hiroshi. AU - Takahara, Kazuhiko. AU - Inaba, Kayo. PY - 2015/12/1. Y1 - 2015/12/1. N2 - Conventional dendritic cells (cDCs) present α-galactosylceramide (αGC) to invariant natural killer T (iNKT) cells through CD1d. Among cDC subsets, CD8+ DCs efficiently induce IFN-γ production in iNKT cells. Using fluorescence-labeled αGC, we showed that CD8+ DCs incorporated larger amounts of αGC and kept it intact longer than CD8- DCs. Histological analyses revealed that Langerin+CD8+ DCs in the splenic marginal zone, which was the unique equipment to capture blood-borne antigens, preferably incorporated αGC, and the depletion of Langerin+ cells decreased IFN-γ and IL-12 production in response to αGC. Furthermore, splenic Langerin+CD8+ DCs expressed more ...
T cell stimulatory capacity of DCs cultured with PGE2. Day-5 DCs were recultured in the absence or presence of PGE2 (10 μM), TNF-α (1,000 U/ml), or PGE2 pl
Myeloid dendritic cells (DCs) are increased in the airway wall of patients with chronic obstructive pulmonary disease (COPD), and postulated to play a crucial role in COPD. However, DC phenotypes in COPD are poorly understood. Function-associated surface molecules on bronchoalveolar lavage fluid (BALF) DCs were analyzed using flow cytometry in current smokers with COPD, in former smokers with COPD and in never-smoking controls. Myeloid DCs of current smokers with COPD displayed a significantly increased expression of receptors for antigen recognition such as BDCA-1 or Langerin, as compared with never-smoking controls. In contrast, former smokers with COPD displayed a significantly decreased expression of these receptors, as compared with never-smoking controls. A significantly reduced expression of the maturation marker CD83 on myeloid DCs was found in current smokers with COPD, but not in former smokers with COPD. The chemokine receptor CCR5 on myeloid DCs, which is also important for the uptake and
Page 2 of 2 - DC (Dendritic-Cell) Isolation - posted in Immunology: Hello Friends,I have just entered into immunology research and I need to know the following: Please try to help me by answering the following questions if you have expertise.1. Whats the reason behind using isotype controls in an experiment? I need the mechanism behind the usage of isotype controls in experiments (often when we go for flow cytometry)?2. What is the principle of using IL-4 and GM-CSF to generate DCs fr...
Immature plasmacytoid dendritic cells are the principal alpha interferon-producing cells (IPC), responsible for primary antiviral immunity. IPC express surface molecules CD4, CCR5, and CXCR4, which are known coreceptors required for human immunodeficiency virus (HIV) infection. Here we show that IPC are susceptible to and replicate HIV type 1 (HIV-1). Importantly, viral replication is triggered upon activation of IPC with CD40 ligand, a signal physiologically delivered by CD4 T cells. Immunohistochemical staining of tonsil from HIV-infected individuals reveals HIV p24+ IPC, consistent with in vivo infection of these cells. IPC exposed in vitro to HIV produce alpha interferon, which partially inhibits viral replication. Nevertheless, IPC efficiently transmit HIV-1 to CD4 T-cells, and such transmission is also augmented by CD40 ligand activation. IPC produce RANTES/CCL5 and MIP-1α/CCL3 when exposed to HIV in vitro. IPC also induce naïve CD4 T cells to proliferate and would therefore ...
Dendritic cells (DCs) are antigen presenting cells that are characterized by a potent capacity to initiate immune responses. DCs comprise several subsets with distinct phenotypes. After sensing any danger(s) to the host via their innate immune receptors such as Toll-like receptors, DCs become mature and subsequently present antigens to CD4+ T cells. Since DCs possess the intrinsic capacity to polarize CD4+ helper cells, it is critical to understand the immunological roles of DCs for clinical applications. Here, we review the different DC subsets, their danger-sensing receptors and immunological functions. Furthermore, the cytokine reporter mouse model for studying DC activation is introduced.
Recently, we delineated the mechanism in which graft-versus-host disease (GVHD), the major detrimental effect of allogeneic bone marrow transplantation, is enhanced by pathogenic colon-derived donor dendritic cells (DC) in a murine model. First, we will find the genetic signature of these DC using RNA sequence assay. Secondly, we will identify the equivalent human DC from post-transplant patients blood sample. The genetic profile of pathogenic colon-derived DC will provide us with a powerful biomarker to predict and treat severe GVHD. ...