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MTOR coordinates transcriptional programs and mitochondrial metabolism of activated Treg subsets to protect tissue homeostasis

ABSTRACT: Regulatory T (Treg) cells derived from the thymus (tTreg) and periphery (pTreg) play central and distinct roles in immunosuppression, but mechanisms governing the generation and activation of Treg subsets in vivo remain uncertain. Here, we report that mechanistic target of rapamycin (mTOR) unexpectedly supports the homeostasis and functional activation of tTreg and pTreg cells. Further, mTOR signaling is crucial for programming activated Treg cell effector function to protect immune tolerance and tissue homeostasis. Treg-specific deletion of mTOR drives spontaneous TH2 responses and altered barrier tissue homeostasis, associated with reductions in both thymic derived effector Treg (eTreg) and pTreg cells. Mechanistically, mTOR acts downstream of antigenic signals to drive IRF4 expression and mitochondrial metabolism, and accordingly, disruption of mitochondrial metabolism severely impairs Treg cell suppressive function and their homeostasis in tissues. Collectively, our results demonstrate that mTOR coordinates transcriptional and metabolic programs in activated Treg subsets to mediate tissue homeostasis

ORGANISM(S): Mus musculus

PROVIDER: GSE104130 | GEO | 2019/09/12

REPOSITORIES: GEO

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