MicroRNA-31 negatively regulates peripherally derived regulatory T-cell generation by repressing retinoic acid-inducible protein 3.
Peripherally derived regulatory T (pT(reg)) cell generation requires T-cell receptor (TCR) signalling and the cytokines TGF-β1 and IL-2. Here we show that TCR signalling induces the microRNA miR-31, which negatively regulates pT(reg)-cell generation. miR-31 conditional deletion results in enhanced induction of pT(reg) cells, and decreased severity of experimental autoimmune encephalomyelitis (EAE). Unexpectedly, we identify Gprc5a as a direct target of miR-31. Gprc5a is known as retinoic acid-inducible protein 3, and its deficiency leads to impaired pT(reg-)cell induction and increased EAE severity. By generating miR-31 and Gprc5a double knockout mice, we show that miR-31 promotes the development of EAE through inhibiting Gprc5a. Thus, our data identify miR-31 and its target Gprc5a as critical regulators for pT(reg)-cell generation, suggesting a previously unrecognized epigenetic mechanism for dysfunctional T(reg) cells in autoimmune diseases.
Zhang, L; Ke, F; Liu, Z; Bai, J; Liu, J; Yan, S; Xu, Z; Lou, F; Wang, H; Zhu, H; Sun, Y; Cai, W; Gao, Y; Li, Q; Yu, X-Z; Qian, Y; Hua, Z; Deng, J; Li, Q-J; Wang, H
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