Metabolic control of T_H17 and induced T_reg cell balance by an epigenetic mechanism.

ABSTRACT: Metabolism has been shown to integrate with epigenetics and transcription to modulate cell fate and function. Beyond meeting the bioenergetic and biosynthetic demands of T-cell differentiation, whether metabolism might control T-cell fate by an epigenetic mechanism is unclear. Here, through the discovery and mechanistic characterization of a small molecule, (aminooxy)acetic acid, that reprograms the differentiation of T helper 17 (T_H17) cells towards induced regulatory T (iT_reg) cells, we show that increased transamination, mainly catalysed by GOT1, leads to increased levels of 2-hydroxyglutarate in differentiating T_H17 cells. The accumulation of 2-hydroxyglutarate resulted in hypermethylation of the Foxp3 gene locus and inhibited Foxp3 transcription, which

SUBMITTER: Xu T 

PROVIDER: S-EPMC6701955 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature