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An activation-induced immunoregulatory and tissue-residency program modulated by c-MAF in human memory Th17 cells [ChIP-seq] [RNA-seq]

ABSTRACT: T cell effector function is largely mediated through the release of pro-inflammatory cytokines that need to be tightly regulated to avoid tissue damage. Here we show that the anti-inflammatory cytokine IL-10 is produced by a subset of recently-activated human Th17 cells and is controlled by the selective up-regulation of the transcription factor c-MAF. In addition, recently-activated IL-10+ Th17 cells upregulate immunoregulatory genes and genes characteristic of tissue resident T cells. In contrast, recently activated IL-10- Th17 cells maintain a pro-inflammatory gene expression profile and upregulate homing receptors to recirculate from tissues to blood. By integrating ChIP-seq and RNA-seq analyses, we demonstrate that c-MAF plays a key role in orchestrating the immune-regulatory and tissue residency program of IL-10+ Th17 cells by binding to a large number of non-promoter regions with enhancer-like features. Thus, c-MAF may represent a relevant factor discriminating between immunoregulatory and pro-inflammatory human Th17 cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE101389 | GEO | 2018/09/12

REPOSITORIES: GEO

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Gene array for identifying molecules involved in IL-10 regulation during Th17 polarization

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