Intronic miR342 is a master regulator of cellular glycolysis in Foxp3+ regulatory CD4 T cells

Foxp3+ regulatory T (Treg) cells are a subset of CD4 T cells that play a potent and indispensable role in regulating immunity and tolerance. The precise mechanisms by which Treg cells mediate such functions have extensively been explored, and there are many cellular and molecular factors that are instrumental for adequate Treg cell functions. miRNAs, small non-coding RNA molecules, are one of the factors capable of modulating Treg cell functions. In this study, we report that miR-342 is essential for Treg cells to mitigate autoimmune inflammation in the central nervous system. Utilizing novel mouse models with Treg cell-specific miR-342 deficiency or overexpression, we demonstrate that miR-342 expression in Treg cells, while dispensable for immune homeostasis at steady-state conditions, is necessary for Treg cells to control inflammatory responses. Mechanistically, we found that Treg cells deficient in miR-342 display dysregulated metabolic programming, elevated glycolysis and decreased oxidative phosphorylation, a metabolic phenotype associated with functionally defective Treg cells. Collectively, our findings uncover that miR-342 may serve a master regulator of Treg cell metabolism and functions.