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Title:
Satb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation | Nature Communications
Description:
The genome organizer, special AT-rich sequence-binding protein-1 (Satb1), plays a pivotal role in the regulation of global gene networks in a cell type-dependent manner and is indispensable for the development of multiple cell types, including mature CD4+ T, CD8+ T, and Foxp3+ regulatory T cells in the thymus. However, it remains unknown how the differentiation and effector program of the Th subsets in the periphery are regulated by Satb1. Here, we demonstrate that Satb1 differentially regulates gene expression profiles in non-pathogenic and pathogenic Th17 cells and promotes the pathogenic effector program of encephalitogenic Th17 cells by regulating GM-CSF via Bhlhe40 and inhibiting PD-1 expression. However, Satb1 is dispensable for the differentiation and non-pathogenic functions of Th17 cells. These results indicate that Satb1 regulates the specific gene expression and function of effector Th17 cells in tissue inflammation. A chromatin remodelling factor Satb1 is essential for T cell lineage development in the thymus. Here the authors show that while Satb1 is dispensable for the differentiation of Th17 cells and their response to gut commensals, it plays a critical role in pathogenic Th17 effector function in EAE by directly activating Bhlhe40 and modulating PD-1.
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nature portfolio privacy policy scientific research granulocyte-macrophage colony-stimulating factor advertising b7-cd28 ligand-receptor family jsps research fellow plate-coated anti-cd3/cd28 nature communications reprints th17 cell-derived tgf-Ξ²1 thermo fisher scientific il17acre r26reyfp satb1fl/fl satb1-dependent super-enhancer establishment full size image il17acre r26reyfp satb1wt/wt rich sequence-binding protein-1 plate-coated anti-cd3 crossed satb1fl/fl mice satb1-mediated gm-csf production thpokcre satb1fl/fl mice dichotomous nature research institute phase ib/iia randomised plate-bound anti-cd3 anti-cd3 monoclonal antibody vitro-polarized th17 cells52 tgf-Ξ² enriched environment cell type-dependent manner class ii mhc thpokcre satb1wt/wt mice gm-csf-targeting treatments th17 cell-mediated disease27 context-dependent gene regulations anti-satb1 monoclonal antibody dna data bank aryl hydrocarbon receptor environmental context-dependent manner original author including gm-csf production permissions il-23-mediated signaling events isotype-matched control antibody satb1-deficient th17 cells satb1-mediated gene expression thpokcre satb1fl/fl naive cd25βcd44low cd4+ barely secreted gm-csf nature 455 nature 535
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headline:Satb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation
description:The genome organizer, special AT-rich sequence-binding protein-1 (Satb1), plays a pivotal role in the regulation of global gene networks in a cell type-dependent manner and is indispensable for the development of multiple cell types, including mature CD4+ T, CD8+ T, and Foxp3+ regulatory T cells in the thymus. However, it remains unknown how the differentiation and effector program of the Th subsets in the periphery are regulated by Satb1. Here, we demonstrate that Satb1 differentially regulates gene expression profiles in non-pathogenic and pathogenic Th17 cells and promotes the pathogenic effector program of encephalitogenic Th17 cells by regulating GM-CSF via Bhlhe40 and inhibiting PD-1 expression. However, Satb1 is dispensable for the differentiation and non-pathogenic functions of Th17 cells. These results indicate that Satb1 regulates the specific gene expression and function of effector Th17 cells in tissue inflammation. A chromatin remodelling factor Satb1 is essential for T cell lineage development in the thymus. Here the authors show that while Satb1 is dispensable for the differentiation of Th17 cells and their response to gut commensals, it plays a critical role in pathogenic Th17 effector function in EAE by directly activating Bhlhe40 and modulating PD-1.
datePublished:2019-02-01T00:00:00Z
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headline:Satb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation
description:The genome organizer, special AT-rich sequence-binding protein-1 (Satb1), plays a pivotal role in the regulation of global gene networks in a cell type-dependent manner and is indispensable for the development of multiple cell types, including mature CD4+ T, CD8+ T, and Foxp3+ regulatory T cells in the thymus. However, it remains unknown how the differentiation and effector program of the Th subsets in the periphery are regulated by Satb1. Here, we demonstrate that Satb1 differentially regulates gene expression profiles in non-pathogenic and pathogenic Th17 cells and promotes the pathogenic effector program of encephalitogenic Th17 cells by regulating GM-CSF via Bhlhe40 and inhibiting PD-1 expression. However, Satb1 is dispensable for the differentiation and non-pathogenic functions of Th17 cells. These results indicate that Satb1 regulates the specific gene expression and function of effector Th17 cells in tissue inflammation. A chromatin remodelling factor Satb1 is essential for T cell lineage development in the thymus. Here the authors show that while Satb1 is dispensable for the differentiation of Th17 cells and their response to gut commensals, it plays a critical role in pathogenic Th17 effector function in EAE by directly activating Bhlhe40 and modulating PD-1.
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