Peripherally derived regulatory T (pTreg) cells are disunctional in autoimmune diseases and their 
generation requires T-cell receptor (TCR) signalling and the cytokines TGF-β1 and IL-2. 

Authors show that TCR signalling induces the microRNA miR-31, which negatively regulates pTreg-cell generation. 

miR-31 conditional deletion results in enhanced induction of pTreg cells, and decreased severity of experimental autoimmune encephalomyelitis (EAE). 

Unexpectedly, authors identify Gprc5a as a direct target of miR-31. Gprc5a is known as retinoic acid-inducible protein 3, and its deficiency leads to impaired pTreg-cell induction and increased EAE severity. 

By generating miR-31 and Gprc5a double knockout mice, authors show that miR-31 promotes the development of EAE through inhibiting Gprc5a. 

Thus, these data identify miR-31 and its target Gprc5a as critical regulators for pTreg-cell generation, suggesting a previously unrecognized epigenetic mechanism for dysfunctional Treg cells in autoimmune diseases.