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Impact of RORgt in regulating CD4 T cells primed under Th17 conditions

ABSTRACT: CD4 T cells are an essential component of antiviral adaptive immune cell responses. Central to the functional capabilities of CD4 T Cells is their ability to differentiate into distinct subsets. Subset differentiation and maintenance is dependent on the coordinated and sequential activation of certain master regulator transcription factors. While antiviral responses are predominantly Th1, prior studies have shown that both T-bet and Eomes, two critical regulators of Th1 responses are dispensable for CD4 T cell mediated protection. CD4 T Cells lacking both T-bet and Eomes produce strong and highly protective Th17 response characterized by high expression of the transcription factor RORγt. Here we determine the impact of RORγt regulation in CD4 T Cells primed under Th17 conditions and also deficient in T-bet and Eomes. Our studies reveal RORγt regulates several hundred genes that in Th17 CD4 T Cells, thus providing a potential molecular framework for targeting protective anti-viral immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE291839 | GEO | 2025/08/26

REPOSITORIES: GEO

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Human LY9 governs CD4+ T-cell IFN-γ immunity to Mycobacterium tuberculosis

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Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells

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Gfi1, a transcriptional repressor, inhibits the induction of the T helper type 1 programme in activated CD4 T cells

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Enhanced Pathogenicity of Th17 cells Generated in the Absence of Transforming Growth Factor-β Signaling

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2010-08-31 | E-GEOD-23505 | biostudies-arrayexpress

Enhanced Pathogenicity of Th17 cells Generated in the Absence of Transforming Growth Factor-β Signaling: ChIPSeq

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2010-08-31 | E-GEOD-23681 | biostudies-arrayexpress

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2013-12-03 | E-GEOD-40623 | biostudies-arrayexpress

Identification of a new pathway for Th1 cell development induced by cooperative stimulation with IL-4 and TGFbeta [Affymetrix]

Project description:IL-4 plays an important role in the induction of Th2 and Th9 cells as well as in the inhibition of Th1 cell generation. We herein show that a combination of IL-4 and TGFbeta augment the development of Th1 cells that express CD103 (CD103+ Th1 cells) if IFNgamma is present. The T-box containing transcription factor, eomesodermin (Eomes) is preferentially expressed in CD103+ Th1 cells, and is involved in IFNgamma production. The induction of T-bet during early T cell activation is essential for the formation of the active chromatin at both the Eomes and IFNgamma gene loci. TGFbeta is required for the induction of Eomes and CD103, as well as the inhibition of Th2 cytokine expression. In addition, IL-4 induces Eomes transcription through activation of the Stat6 signaling pathway. IFNgamma-producing CD103+ Th1 cells are detected in the IEL of normal mice, and their numbers significantly decrease in Tbet- and Stat6-deficient mice. These results represent the first molecular mechanism of IL-4/TGFbeta-dependent augmentation of Th1 cell generation, and raise the possibility that IL-4 and TGFbeta may simultaneously enhance the Th1 cell-mediated immune responses under certain cytokine conditions. CD103+ Th1 and Th1 cells are profiled for mRNA expression

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Identification of a new pathway for Th1 cell development induced by cooperative stimulation with IL-4 and TGFbeta [Agilent]

Project description:IL-4 plays an important role in the induction of Th2 and Th9 cells as well as in the inhibition of Th1 cell generation. We herein show that a combination of IL-4 and TGFbeta augment the development of Th1 cells that express CD103 (CD103+ Th1 cells) if IFNgamma is present. The T-box containing transcription factor, eomesodermin (Eomes) is preferentially expressed in CD103+ Th1 cells, and is involved in IFNgamma production. The induction of T-bet during early T cell activation is essential for the formation of the active chromatin at both the Eomes and IFNgamma gene loci. TGFbeta is required for the induction of Eomes and CD103, as well as the inhibition of Th2 cytokine expression. In addition, IL-4 induces Eomes transcription through activation of the Stat6 signaling pathway. IFNgamma-producing CD103+ Th1 cells are detected in the IEL of normal mice, and their numbers significantly decrease in Tbet- and Stat6-deficient mice. These results represent the first molecular mechanism of IL-4/TGFbeta-dependent augmentation of Th1 cell generation, and raise the possibility that IL-4 and TGFbeta may simultaneously enhance the Th1 cell-mediated immune responses under certain cytokine conditions. Th9+IFNgamma and Th9 cells are profiled for mRNA expression

2012-03-17 | E-GEOD-36554 | biostudies-arrayexpress

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