Abstract 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. microRNAs, small noncoding RNA molecules, are one of the factors capable of regulating 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 and allergic airway inflammation in the lung. 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 profiles, elevated glycolysis and decreased oxidative phosphorylation, a metabolic phenotype associated with functionally defective Treg cells. Interestingly, miR-342–dependent metabolic dysregulation was observed in Treg but not in T helper 1–type cells. In support, miR-342–mediated Rictor targeting was found in Treg but not in T helper 1–type cells. Last, Treg cells overexpressing miR-342 were able to effectively suppress ongoing autoimmune inflammation in an adoptive Treg transfer but not in active disease model. Collectively, our findings uncover that miR-342 may serve a key regulator specific for metabolism and functions in Treg cells.
Yu et al. (Wed,) studied this question.