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RORα is critical for mTORC1 activity in T cell-mediated colitis [ChIP-seq]

ABSTRACT: Inflammatory bowel disease (IBD) is multi-factorial chronic intestinal inflammation driven by pathogenic T cells. The mechanisms underlying colitis pathogenicity and anti-TNF therapy resistance are not fully understood. Here we demonstrate that RORα is highly expressed in active UC patients, particularly in those non-responsive to anti-TNF treatment. Rorα deficient CD4+ T cells could not induce severe gut inflammation in a T cell transfer colitis model. Mechanistically, RORα regulated T cell infiltration in colon by promoting T cell migration and inhibiting T cell apoptosis. Meanwhile, genome-wide occupancy and transcriptome analysis revealed that RORα promoted mTORC1 activation. mTORC1 signaling, also hyperactivated in active UC patients, was necessary for T cell-mediated colitis.

ORGANISM(S): Mus musculus

PROVIDER: GSE168217 | GEO | 2021/07/28

REPOSITORIES: GEO

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