Gene expression profiling of Th17, Th1*, Treg cells in the spinal cord of EAE mice , and Th17, Treg cells in the SILP of SFB colonized mice
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PROVIDER: PRJNA589652 | ENA |
REPOSITORIES: ENA
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Project description:The goal of the RNAseq experiment is to compare gene expression of T cells in different microenvironments. We hypothesized that same T cell subtype (Th17/Th1* cells, or Treg cells in this study) need to change gene expression to adapt to different microenvironments (spinal cord in EAE mice VS. SILP in SFB-colonized mice). By profiling and comparing gene expression of these cells, we were able to identify candidate genes that enable cells for tissue adaptation for functional study.
2020-07-01 | GSE140422 | GEO
Project description:There are two aims in this study – (1) To figure out the pathogenic sub-populations of CD4+ T cells in the spinal cord of EAE model; and (2) by comparing the gene expression profile of pathogenic Th17 cells in EAE model to that of the non-pathogenic Th17 cells induced by SFB in SILP, to identify genes candidates that are potentially selectively essential to pathogenic ones.
2020-07-01 | GSE140468 | GEO
Project description:Purpose: The goal of this study is to identify gut dendritic cells that induces CD4 Th17 cells that play an critical role in mucosal immunity Methods: C57BL/6 mice were orally gavaged with fecal material derived from SFB-positive donor mice. Five days post oral gavage, mesenteric lymph nodes were harvested and dendritic cells were FACS-sorted. cDNA library from migratory dendritic cells (MHCII-highCD11c+) and resident dendritic cells (MHCII+CD11c-high) were generated using Chromium Single Cell 3' Library v2 Kit (10x Genomics). RNA sequencing was performed using NovaSeq S4 flow cell (Illumina). Data was processed using the Cell Ranger software (10x Genomics) followed by analysis using the R-based package Seurat. Results: Gut colonization with SFB increased the migration of type 2 but not type 1 dendritic cells to the mesenteric lymph nodes. Based on transcriptomic profiles, migratory type 2 dendritic cells consist of 2 major cell clusters (Cd40-Ccl22 and Cd1d1-Tnfrsf4-enriched cells). The Th17 response inducing cytokine IL-6 co-localized with the Cd40-Ccl22-expressing cells. Conclusion: Our study represents the first to carefully characterize the mucosal dendritic cells at steady state and during acute CD4 Th17 response. Transcriptomic profiling enabled the subsetting of dendritic cells based on functional markers (such as cytokines and chemokines) that are otherwise difficult to measure at the protein level. These results provide a focused look at mucosal dendritic cells and their roles in dictating different T cell responses.
2022-07-13 | GSE184423 | GEO
Project description:Upon antigen stimulation, the bioenergetic demands of T cells increase dramatically over the resting state. Although a role for the metabolic switch to glycolysis has been suggested to support increased anabolic activities and facilitate T cell growth and proliferation, whether cellular metabolism controls T cell lineage choices remains poorly understood. Here we report that the glycolytic pathway is actively regulated during the differentiation of inflammatory TH17 and Foxp3-expressing regulatory T cells (Treg), and controls cell fate determination. TH17 but not Treg-inducing conditions resulted in strong upregulation of the glycolytic activity and induction of glycolytic enzymes. Blocking glycolysis inhibited TH17 development while promoting Treg cell generation. Moreover, the transcription factor hypoxia-inducible factor 1a (HIF1a) was selectively expressed in TH17 cells and its induction required signaling through mTOR, a central regulator of cellular metabolism. HIF1a-dependent transcriptional program was important for mediating glycolytic activity, thereby contributing to the lineage choices between TH17 and Treg cells. Lack of HIF1a resulted in diminished TH17 development but enhanced Treg differentiation, and protected mice from autoimmune CNS inflammation. Our studies demonstrate that HIF1a-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. Naïve CD4 T cells from wild-type and HIF1a-deficient mice (in triplicates each group) were differentiated under TH17 conditions for 2.5 days, and RNA was analyzed by microarrays.
2011-06-07 | E-GEOD-29765 | biostudies-arrayexpress
Project description:In this study, the participation of fetal factors in maintaining the immune balance during gestation was investigated by assessing the effects of human chorionic gonadotropin (hCG) on murine Treg cells and Th17 cells.
2022-10-14 | PXD035883 | Pride
Project description:Interventions: DEX: a loading dosage of dexmedetomidine (0.5 ug/Kg) was infused introvenously 10 min before anesthesia and followed continously at0.5 ug/Kg/h for 2h;control:saline
Primary outcome(s): interleukin-17, 6, 23, 10, 1ß, TNF-a, TGFß-1, HMGB1, Th17/Treg cell count
Study Design: Randomized parallel controlled trial
| 2663054 | ecrin-mdr-crc
Project description:The gastrointestinal tract of mammals is inhabited by hundreds of distinct species of commensal microorganisms that exist in a mutualistic relationship with the host. The process by which the commensal microbiota influence the host immune system is poorly understood. We show here that colonization of the small intestine of mice with a single commensal microbe, segmented filamentous bacterium (SFB), is sufficient to induce the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere tightly to the surface of epithelial cells in the terminal ileum of mice with Th17 cells but are absent from mice that have few Th17 cells. Colonization with SFB was correlated with increased expression of genes associated with inflammation, anti-microbial defenses, and tissue repair, and resulted in enhanced resistance to the intestinal pathogen Citrobacter rodentium. Control of Th17 cell differentiation by SFB may thus establish a balance between optimal host defense preparedness and potentially damaging T cell responses. Manipulation of this commensal-regulated pathway may provide new opportunities for enhancing mucosal immunity and treating autoimmune disease.
2009-10-22 | GSE18348 | GEO
Project description:The gastrointestinal tract of mammals is inhabited by hundreds of distinct species of commensal microorganisms that exist in a mutualistic relationship with the host. The process by which the commensal microbiota influence the host immune system is poorly understood. We show here that colonization of the small intestine of mice with a single commensal microbe, segmented filamentous bacterium (SFB), is sufficient to induce the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere tightly to the surface of epithelial cells in the terminal ileum of mice with Th17 cells but are absent from mice that have few Th17 cells. Colonization with SFB was correlated with increased expression of genes associated with inflammation, anti-microbial defenses, and tissue repair, and resulted in enhanced resistance to the intestinal pathogen Citrobacter rodentium. Control of Th17 cell differentiation by SFB may thus establish a balance between optimal host defense preparedness and potentially damaging T cell responses. Manipulation of this commensal-regulated pathway may provide new opportunities for enhancing mucosal immunity and treating autoimmune disease. Experiment Overall Design: We compared the gene expression profiles in the terminal ileum of Swiss-Webster GF mice before and after colonization with SFB, which induced robust Th17 cell differentiation. To sieve out host effects, the role of other microbiota, as well as other factors, we also evaluated the transcriptional program induced in Jackson C57BL/6 mice after co-housing with Taconic B6 animals, which also induces Th17 cell differentiation. 0.5 cm of the most distal part of the small intestine was dissected. Total RNA was extracted with TRIzol. RNA was labeled and hybridized to GeneChip Mouse Genome 430 2.0 arrays following the Affymetrix protocols. Data were analyzed in GeneSpring GX10.
2009-11-10 | E-GEOD-18348 | biostudies-arrayexpress
Project description:An imbalance of T helper (Th17) cells and regulatory T (Treg) cells contributes to the pathogenesis of autoimmune diseases. The endogenous metabolite itaconate (ITA) is a regulator of macrophages; however, its role in T cells regulation is unclear. Here, we show that ITA inhibited Th17 cell differentiation and promoted Treg cell differentiation via metabolic and epigenetic reprogramming. Mechanistically, ITA suppressed glycolysis and mitochondrial respiration in Th17 and Treg-polarizing T cells. In Th17 cells, the S-adenosyl-L-methionine/ S-adenosylhomocysteine ratio was decreased following ITA administration in vitro, subsequently altering the epigenetic status. Further, ITA inhibited RORγt binding at the Il17a promoter, resulting in reduced IL-17A expression. In Treg cells, ITA reduced 2-hydroxyglutarate levels, which suppressed Foxp3 expression. The adoptive transfer of ITA-treated Th17-polarizing T cells ameliorated experimental autoimmune encephalomyelitis. Collectively, these results indicate that ITA serves as a crucial metabolic regulator for Th17/Treg cell balance and a potential therapeutic agent against autoimmune diseases.
2023-01-18 | GSE182895 | GEO
Project description:Upon antigen stimulation, the bioenergetic demands of T cells increase dramatically over the resting state. Although a role for the metabolic switch to glycolysis has been suggested to support increased anabolic activities and facilitate T cell growth and proliferation, whether cellular metabolism controls T cell lineage choices remains poorly understood. Here we report that the glycolytic pathway is actively regulated during the differentiation of inflammatory TH17 and Foxp3-expressing regulatory T cells (Treg), and controls cell fate determination. TH17 but not Treg-inducing conditions resulted in strong upregulation of the glycolytic activity and induction of glycolytic enzymes. Blocking glycolysis inhibited TH17 development while promoting Treg cell generation. Moreover, the transcription factor hypoxia-inducible factor 1a (HIF1a) was selectively expressed in TH17 cells and its induction required signaling through mTOR, a central regulator of cellular metabolism. HIF1a-dependent transcriptional program was important for mediating glycolytic activity, thereby contributing to the lineage choices between TH17 and Treg cells. Lack of HIF1a resulted in diminished TH17 development but enhanced Treg differentiation, and protected mice from autoimmune CNS inflammation. Our studies demonstrate that HIF1a-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells.
2011-06-07 | GSE29765 | GEO