Satb1 directs the differentiation of TH17 cells through suppression of IL-2 expression
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PROVIDER: PRJNA1054562 | ENA |
REPOSITORIES: ENA
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Project description:TH17 cells play an important role in host defense especially in barrier organs. Altered functionality of TH17 cells is associated with dysregulated tissue homeostasis resulting in an increased susceptibility for the development of autoimmune diseases. Thus, it is critical to identify mechanisms governing physiological as well as pathophysiological TH17 cell differentiation and identify strategies targeting TH17 cell differentiation in disease settings. Here, we identified the genome organizer Special AT-rich sequence-binding protein 1 (Satb1) as a pioneering factor for TH17 cell development. Satb1 is highly expressed in TH17 cells and loss of Satb1 prevents the differentiation of TH17 cells. As a consequence, expression of Satb1 in CD4+ T cells is required for the formation of TH17 cell-driven autoimmune diseases. Mechanistically, Satb1 mediates TH17 cell development through regulating accessibility of the Il2 gene locus and thereby preventing IL-2 signaling early during TH17 cell differentiation. Thus, Satb1 is critical by suppressing IL-2 expression during the formation of TH17 cells and may be a novel therapeutic target for the treatment of TH17 cell-driven autoimmune diseases
2025-05-20 | GSE290258 | GEO
Project description:Satb1 directs the differentiation of TH17 cells through suppression of IL-2 expression [scMultiom ATAC/RNA-seq]
| PRJNA1226664 | ENA
Project description:TH17 cells play an important role in host defense especially in barrier organs. Altered functionality of TH17 cells is associated with dysregulated tissue homeostasis resulting in an increased susceptibility for the development of autoimmune diseases. Thus, it is critical to identify mechanisms governing physiological as well as pathophysiological TH17 cell differentiation and identify strategies targeting TH17 cell differentiation in disease settings. Here, we identified the genome organizer Special AT-rich sequence-binding protein 1 (Satb1) as a pioneering factor for TH17 cell development. Satb1 is highly expressed in TH17 cells and loss of Satb1 prevents the differentiation of TH17 cells. As a consequence, expression of Satb1 in CD4+ T cells is required for the formation of TH17 cell-driven autoimmune diseases. Mechanistically, Satb1 mediates TH17 cell development through regulating accessibility of the Il2 gene locus and thereby preventing IL-2 signaling early during TH17 cell differentiation. Thus, Satb1 is critical by suppressing IL-2 expression during the formation of TH17 cells and may be a novel therapeutic target for the treatment of TH17 cell-driven autoimmune diseases.
2025-05-20 | GSE250577 | GEO
Project description:TH17 cells play an important role in host defense especially in barrier organs. Altered functionality of TH17 cells is associated with dysregulated tissue homeostasis resulting in an increased susceptibility for the development of autoimmune diseases. Thus, it is critical to identify mechanisms governing physiological as well as pathophysiological TH17 cell differentiation and identify strategies targeting TH17 cell differentiation in disease settings. Here, we identified the genome organizer Special AT-rich sequence-binding protein 1 (Satb1) as a pioneering factor for TH17 cell development. Satb1 is highly expressed in TH17 cells and loss of Satb1 prevents the differentiation of TH17 cells. As a consequence, expression of Satb1 in CD4+ T cells is required for the formation of TH17 cell-driven autoimmune diseases. Mechanistically, Satb1 mediates TH17 cell development through regulating accessibility of the Il2 gene locus and thereby preventing IL-2 signaling early during TH17 cell differentiation. Thus, Satb1 is critical by suppressing IL-2 expression during the formation of TH17 cells and may be a novel therapeutic target for the treatment of TH17 cell-driven autoimmune diseases.
2025-05-20 | GSE250576 | GEO
Project description:Interleukin 23 (IL-23) triggers pathogenic features in pro-inflammatory, IL-17-secreting T cells (Th17 and Tγδ17) that play a key role in the development of inflammatory diseases. However, the IL-23 signaling cascade remains largely undefined. Here we used quantitative phosphoproteomics to characterize IL-23 signaling in primary murine Th17 cells. We quantified 6,888 phosphorylation sites in Th17 cells, and found 168 phosphorylations regulated upom IL-23 stimulation. IL-23 increased the phosphorylation of the myosin regulatory light chain (RLC), an actomyosin contractibility marker, in Th17 and Tγδ cells. IL-23-induced RLC phosphorylation required JAK2 and ROCK catalytic activity, and the study of the IL-23/ROCK axis revealed an unexpected role of IL-23 in the migration of Tγδ17 and Th17 cells. Moreover, pharmacological inhibition of ROCK reduced Tγδ17 recruitment to inflamed skin upon challenge with inflammatory agent Imiquimod. This work: i) provides new insights into phosphorylation networks that control Th17 cells, ii) widely expands the current knowledge on IL-23 signaling, and iii) contributes to the increasing list of immune cells subsets characterized by global phosphoproteomic approaches.
2020-03-25 | PXD016633 | Pride
Project description:TH17 cells play an important role in host defense especially in barrier organs. Altered functionality of TH17 cells is associated with dysregulated tissue homeostasis resulting in an increased susceptibility for the development of autoimmune diseases. Thus, it is critical to identify mechanisms governing physiological as well as pathophysiological TH17 cell differentiation and identify strategies targeting TH17 cell differentiation in disease settings. Here, we identified the genome organizer Special AT-rich sequence-binding protein 1 (Satb1) as a pioneering factor for TH17 cell development. Satb1 is highly expressed in TH17 cells and loss of Satb1 prevents the differentiation of TH17 cells. As a consequence, expression of Satb1 in CD4+ T cells is required for the formation of TH17 cell-driven autoimmune diseases. Mechanistically, Satb1 mediates TH17 cell development through regulating accessibility of the Il2 gene locus and thereby preventing IL-2 signaling early during TH17 cell differentiation. Thus, Satb1 is critical by suppressing IL-2 expression during the formation of TH17 cells and may be a novel therapeutic target for the treatment of TH17 cell-driven autoimmune diseases
2025-05-20 | GSE250578 | GEO
Project description:RNA-seq of Satb1 conditional KO in CD4+ na ve T cells reveals role of Satb1 in developing Th17 T cells through suppression of IL-2 expression
| PRJNA1054567 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-05-20 | GSE250579 | GEO
Project description:Interleukin 17 (IL-17) producing T helper 17 (Th17) cells are critical drivers of pathogenesis in a variety of autoimmune and inflammatory diseases. Strategies to mitigate excessive Th17 response thus remain an attractive target for immunotherapies. Here we report that Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) regulates IL-17 production by Th17 cells in human and mouse. Using CIP2A knock-out (KO) mice and siRNA-mediated CIP2A silencing in human primary CD4+ T cells, we demonstrated that CIP2A silencing results in a significant increase in IL-17 production. Interestingly, CIP2A deficient Th17 cells were characterized by increased strength and duration of STAT3 (Y705) phosphorylation. Genome-wide gene expression profile as well as the p-STAT3 (Y705) interactome of CIP2A deficient Th17 cells identified that CIP2A regulates the strength of the interaction between Acylglycerol kinase (AGK) and STAT3, and thereby, modulates STAT3 phosphorylation as well as expression of IL-17 in Th17 cells. Our results uncover the physiological function of CIP2A in Th17 cells and provides new opportunities for therapeutic intervention in Th17 cell mediated diseases.
2020-05-26 | PXD010612 | Pride
Project description:IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. Gene array analysis on Stat6 and T-bet double deficient Th17 cells identified the Th2 transcription factor c-Maf to be synergistically up-regulated by IL-6 plus TGFbeta, and associated with Th17 IL-10 production. Both c-Maf and IL-10 induction during Th17 polarization depended on Stat3, but not Stat6 or Stat1, and mechanistically differed from IL-10 regulation by Th2 or IL-27 signals. TGFbeta was also synergistic with IL-27 to induce c-Maf, and induced Stat1 independent IL-10 expression in contrast to IL-27 alone. Retroviral transduction of c-Maf was able to induce IL-10 expression in Stat6 deficient CD4 and CD8 T cells, and c-Maf directly transactivated IL-10 gene expression through binding to a MARE motif in the IL-10 promoter. Together, these data reveal a novel role for c-Maf in regulating T effector development, and suggest that TGFbeta may antagonize Th17 immunity by IL-10 production through c-Maf induction. Our recent studies showed that IL-6 combined with TGFbeta differed from IL-6 combined with IL-23 for IL-10 production and pathogenic activities in CD4 T cells deficient in Stat6 and T-bet, despite similar IL-17 production. We performed gene array analysis on Stat6 and T-bet double deficient cells. We rationalized that by comparing gene expression in cells treated with IL-6 plus TGFbeta versus TGFbeta alone, we would be able to identify genes specific for standard Th17 polarization, and responsible for both IL-17 and IL-10 expression. By next comparing gene expression in cells treated with IL-6 plus TGFbeta versus IL-6 plus IL-23, we could eliminate molecules involved solely in IL-17 regulation, and obtain genes specifically responsible for IL-10 regulation.
2009-03-03 | E-GEOD-15029 | biostudies-arrayexpress