Interleukin-17 producing cells in swine induced by microbiota during the early postnatal period - a brief research report
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ABSTRACT:
SUBMITTER: Stepanova H
PROVIDER: S-EPMC10548118 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:The gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying that Prevotella heparinolytica promotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression. IL-17 induced STAT3 phosphorylation in murine plasma cells, and activated eosinophils. Treatment of Vk*MYC mice with antibodies blocking IL-17, IL-17RA, and IL-5 reduced BM accumulation of Th17 cells and eosinophils and delayed disease progression. Thus, in Vk*MYC mice, commensal bacteria appear to unleash a paracrine signaling network between adaptive and innate immunity that accelerates progression to MM, and can be targeted by already available therapies.
| S-EPMC6277390 | biostudies-literature
Project description:ObjectiveTh17 cells and interleukin-17 (IL-17) cytokine family members are implicated in the pathogenesis of many rheumatic diseases. Most studies in mouse models of inflammatory arthritis have demonstrated a key role for the proinflammatory cytokine IL-17A and its receptor, the IL-17 receptor (IL-17R) A/C heterodimer. The aim of this study was to use a rigorous genetic approach to evaluate the contribution of Th17 cells and IL-17 in the autoantibody-dependent KRN T cell receptor-transgenic mouse model of arthritis.MethodsWe bred KRN mice expressing the major histocompatibility complex class II molecule A(g7) (referred to as K/B/g7 mice) and genetically lacking the related cytokines IL-17A and IL-17F or their critical receptor subunit, IL-17RA. Using bone marrow transplantation, we generated mice in which hematopoietic cells from K/B/g7 donor mice lacked the key Th17-differentiating transcription factor, retinoic acid receptor-related orphan nuclear receptor γt (Rorγt).ResultsK/B/g7 mice lacking both IL-17A and IL-17F produced normal titers of pathogenic autoantibodies, and arthritis developed in a typical manner. Similarly, neither IL-17RA nor Rorγt expression by hematopoietic cells was required for disease development in this model.ConclusionDespite prior reports suggesting that Th17 cells and IL-17A are crucially involved in the pathogenesis of arthritis in K/BxN mice, the results presented here provide genetic evidence that IL-17A and IL-17F, IL-17RA, and Rorγt expression by hematopoietic cells are dispensable for normal arthritis progression in the K/B/g7 mouse model system. We discuss potential explanations for the discrepancies between these 2 highly similar model systems. These findings plus those in other mouse models of arthritis provide insight regarding why therapeutic biologic agents targeting the Th17/IL-17 axis are beneficial in some human rheumatic diseases but not others.
| S-EPMC4963273 | biostudies-literature
Project description:Biomaterials induce an immune response and mobilization of macrophages, yet identification and phenotypic characterization of functional macrophage subsets in vivo remain limited. We performed single-cell RNA sequencing analysis on macrophages sorted from either a biologic matrix [urinary bladder matrix (UBM)] or synthetic biomaterial [polycaprolactone (PCL)]. Implantation of UBM promotes tissue repair through generation of a tissue environment characterized by a T helper 2 (TH2)/interleukin (IL)-4 immune profile, whereas PCL induces a standard foreign body response characterized by TH17/IL-17 and fibrosis. Unbiased clustering and pseudotime analysis revealed distinct macrophage subsets responsible for antigen presentation, chemoattraction, and phagocytosis, as well as a small population with expression profiles of both dendritic cells and skeletal muscle after UBM implantation. In the PCL tissue environment, we identified a CD9hi+IL-36γ+ macrophage subset that expressed TH17-associated molecules. These macrophages were virtually absent in mice lacking the IL-17 receptor, suggesting that they might be involved in IL-17-dependent immune and autoimmune responses. Identification and comparison of the unique phenotypical and functional macrophage subsets in mouse and human tissue samples suggest broad relevance of the new classification. These distinct macrophage subsets demonstrate previously unrecognized myeloid phenotypes involved in different tissue responses and provide targets for potential therapeutic modulation in tissue repair and pathology.
| S-EPMC7549193 | biostudies-literature
Project description:T cells that encounter cultured ocular pigment epithelial cells in vitro are inhibited from undergoing T cell receptor-triggered activation. Because retinal pigment epithelial (RPE) cells are able to suppress T-cell activation, we studied whether RPE cells could suppress cytokine production by activated T helper (Th) cells. In this study we showed that primary cultured RPE cells greatly suppressed activation of bystander CD4+ T cells in vitro, especially the cytokine production by the target T helper cells (Th1 cells, Th2 cells, Th17 cells, but not Th3 cells). Cultured RPE cells and RPE-supernatants significantly suppressed IL-17 producing CD4+ T cells, and RPE cells fully suppressed polarized Th17 cell lines that induced by recombinant proteins, IL-6 and TGFb2. Moreover, RPE cells failed to suppress IL-17 producing T cells in the presence of rIL-6. In addition, Th17 cells exposed to RPE were suppressed via TGFb, which produce RPE cells. These results indicate that retinal PE cells have immunosuppressive capacity in order to inhibit Th17-type effector T cells. Thus, ocular resident cells play a role in establishing immune regulation in the eye. Retinal pigment epithelium suppresses Th17 cells
2012-07-11 | E-GEOD-22877 | biostudies-arrayexpress
Project description:T cells that encounter cultured ocular pigment epithelial cells in vitro are inhibited from undergoing T cell receptor-triggered activation. Because retinal pigment epithelial (RPE) cells are able to suppress T-cell activation, we studied whether RPE cells could suppress cytokine production by activated T helper (Th) cells. In this study we showed that primary cultured RPE cells greatly suppressed activation of bystander CD4+ T cells in vitro, especially the cytokine production by the target T helper cells (Th1 cells, Th2 cells, Th17 cells, but not Th3 cells). Cultured RPE cells and RPE-supernatants significantly suppressed IL-17 producing CD4+ T cells, and RPE cells fully suppressed polarized Th17 cell lines that induced by recombinant proteins, IL-6 and TGFb2. Moreover, RPE cells failed to suppress IL-17 producing T cells in the presence of rIL-6. In addition, Th17 cells exposed to RPE were suppressed via TGFb, which produce RPE cells. These results indicate that retinal PE cells have immunosuppressive capacity in order to inhibit Th17-type effector T cells. Thus, ocular resident cells play a role in establishing immune regulation in the eye.
2012-07-12 | GSE22877 | GEO
Project description:Biomaterials induce an immune response and mobilization of macrophages, yet identification and phenotypic characterization of functional macrophage subsets in vivo remain limited. We performed single-cell RNA sequencing analysis on macrophages sorted from either a biologic matrix [urinary bladder matrix (UBM)] or synthetic biomaterial [polycaprolactone (PCL)]. Implantation of UBM promotes tissue repair through generation of a tissue environment characterized by a T helper 2 (Th2)/interleukin (IL)–4 immune profile, whereas PCL induces a standard foreign body response characterized by Th17/IL-17 and fibrosis. Unbiased clustering and pseudotime analysis revealed distinct macrophage subsets responsible for antigen presentation, chemoattraction, and phagocytosis, as well as a small population with expression profiles of both dendritic cells and skeletal muscle after UBM implantation. In the PCL tissue environment, we identified a CD9 hi+ IL-36y + macrophage subset that expressed Th17-associated molecules. These macrophages were virtually absent in mice lacking the IL-17 receptor, suggesting that they might be involved in IL-17–dependent immune and autoimmune responses. Identification and comparison of the unique phenotypical and functional macrophage subsets in mouse and human tissue samples suggest broad relevance of the new classification. These distinct macrophage subsets demonstrate previously unrecognized myeloid phenotypes involved in different tissue responses and provide targets for potential therapeutic modulation in tissue repair and pathology.
2019-10-10 | GSE138027 | GEO
Project description:Background & aimsSubsets of leukocytes synergize with regenerative growth factors to promote hepatic regeneration. γδT cells are early responders to inflammation-induced injury in a number of contexts. We investigated the role of γδT cells in hepatic regeneration using mice with disruptions in Tcrd (encodes the T-cell receptor δ chain) and Clec7a (encodes C-type lectin domain family 7 member a, also known as DECTIN1).MethodsWe performed partial hepatectomies on wild-type C57BL/6, CD45.1, Tcrd(-/-), or Clec7a(-/-) mice. Cells were isolated from livers of patients and mice via mechanical and enzymatic digestion. γδT cells were purified by fluorescence-activated cell sorting.ResultsIn mice, partial hepatectomy up-regulated expression of CCL20 and ligands of Dectin-1, which was associated with recruitment and activation of γδT cells and their increased production of interleukin (IL)-17 family cytokines. Recruited γδT cells induced production of IL-6 by antigen-presenting cells and suppressed expression of interferon gamma by natural killer T cells, promoting hepatocyte proliferation. Absence of IL-17-producing γδT cells or deletion of Dectin-1 prevented development of regenerative phenotypes in subsets of innate immune cells. This slowed liver regeneration and was associated with reduced expression of regenerative growth factors and cell cycle regulators. Conversely, exogenous administration of IL-17 family cytokines or Dectin-1 ligands promoted regeneration. More broadly, we found that γδT cells are required for inflammatory responses mediated by IL-17 and Dectin-1.ConclusionsγδT cells regulate hepatic regeneration by producing IL-22 and IL-17, which have direct mitogenic effects on hepatocytes and promote a regenerative phenotype in hepatic leukocytes, respectively. Dectin-1 ligation is required for γδT cells to promote hepatic regeneration.
| S-EPMC4123443 | biostudies-literature
Project description:Since their recent discovery, T helper 17 (Th17) cells have been frequently detected in the tumor microenvironment of many malignancies, but their clinical implications remain largely unknown. Interleukin-17 (IL-17) detection is commonly related with poor outcomes in colorectal cancers, yet its presence is associated with antitumor responses in ovarian carcinomas. Numerous experimental models illustrate the divergent roles of Th17 cells in tumor immunity, which appears to be mainly dependent on the tumor context (type, location, and stage of cancer). It is recognized that IL-17 is produced by a variety of cell types and that Th17 cells are endowed with a unique functional plasticity. Therefore, when trying to elucidate potential immune biomarkers and immunotargets, it is extremely important to make a clear dissociation between strategies targeting Th17 versus its hallmark cytokine, IL-17. In this review, we will summarize the data regarding the detection of IL-17 and Th17 in human cancers, consider the experimental evidence on their respective roles in antitumor activity, and discuss the potential of IL-17 as an immune target for therapeutic interventions.
| S-EPMC4918233 | biostudies-literature
Project description:Interleukin-17 (IL-17)-mediated immune responses play a crucial role in the mucosal host defence against microbial and fungal pathogens. However, the chronic activation of IL-17-producing T helper cells can cause autoimmune disease. In addition, recent studies have highlighted key roles of innate cell-mediated IL-17 responses in various inflammatory settings. Besides inflammation, there have also been intriguing findings regarding the involvement of IL-17 responses in the pathogenesis of cardiovascular diseases and tumour formation. Here, we discuss the latest discoveries in regulation and function of innate and adaptive IL-17-producing cells.
| S-EPMC3271338 | biostudies-other
Project description:BackgroundThe intestinal microbiota plays a crucial role in human health, which could affect host immunity and the susceptibility to infectious diseases. However, the role of intestinal microbiota in the immunopathology of invasive candidiasis remains unknown.MethodsIn this work, an antibiotic cocktail was used to eliminate the intestinal microbiota of conventional-housed (CNV) C57/BL6 mice, and then both antibiotic-treated (ABX) mice and CNV mice were intravenously infected with Candida albicans to investigate their differential responses to infection. Furthermore, fecal microbiota transplantation (FMT) was applied to ABX mice in order to assess its effects on host immunity against invasive candidiasis after restoring the intestinal microbiota, and 16S ribosomal RNA gene sequencing was conducted on fecal samples from both uninfected ABX and CNV group of mice to analyze their microbiomes.ResultsWe found that ABX mice displayed significantly increased weight loss, mortality, and organ damage during invasive candidiasis when compared with CNV mice, which could be alleviated by FMT. In addition, the level of IL-17A in ABX mice was significantly lower than that in the CNV group during invasive candidiasis. Treatment with recombinant IL-17A could improve the survival of ABX mice during invasive candidiasis. Besides, the microbial diversity of ABX mice was significantly reduced, and the intestinal microbiota structure of ABX mice was significantly deviated from the CNV mice.ConclusionsOur data revealed that intestinal microbiota plays a protective role in invasive candidiasis by enhancing IL-17A production in our model system.
| S-EPMC7251893 | biostudies-literature