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Transcriptional programing of helper T cell metabolism by the IL-2-STAT5 axis

ABSTRACT: Activated lymphocytes adapt their metabolism to meet the energetic and biosynthetic demands imposed by rapid growth and proliferation. Common gamma chain (c ) family cytokines are central to this process but the role of downstream STAT5 signaling, a cardinal feature of all members, remains loosely defined. Using genome-, transcriptome- and metabolome-wide analyses, we demonstrate that STAT5 is a master regulator of energy and amino acid metabolism in CD4+ ‘helper’ T cells. Mechanistically, we find that STAT5 localizes to a suite of enhancers and promoters for genes encoding essential, often rate-limiting enzymes and transporters, where it instructs transcription through p300 recruitment and epigenetic remodeling. We also find that STAT5 licenses the activity of other metabolic agents downstream of IL-2, namely the mTOR signaling pathway and the transcription factor, MYC, and present evidence for genome-wide cooperation between STAT5 and MYC in both normal and transformed T cells. Taken together, our data provide a molecular framework for transcriptional programing of T cell metabolism downstream of c cytokines and emphasize the Jak-STAT pathway in powering cellular growth and proliferation.

ORGANISM(S): Mus musculus

PROVIDER: GSE207265 | GEO | 2022/10/03

REPOSITORIES: GEO

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