MiR-21 Regulates Metabolic Adaptation of TH17 Cells during Autoimmunity and Host Defence

TH17 cells exhibit great heterogeneity and variable functional states in vivo. However, metabolic adaptation of TH17 cells in vivo and its regulation during autoimmunity and host defence is unknown. Here we report that TH17 cells derived in vivo under homeostatic or autoimmune condition show discrete metabolic states. Metabolic states of TH17 cells in vivo were controlled at the epigenetic level, with conserved regulatory region of key metabolic genes show distinct chromatin accessibility as demonstrated by global chromatin landscape profiling. Mechanistically key regulatory region of a group of microRNAs were shown to be with increased chromatin openness under autoimmune condition, and miR-21 was identified as an essential metabolic regulator of TH17 cells. Understanding the regulation of TH17 cell metabolic adaptation in vivo may therefore provide more defined therapeutic intervention to TH17 cell mediated autoimmune diseases and insights into TH17 cell mediated host defence.