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MicroRNA 182 inhibits CD4(+)CD25(+)Foxp3(+) Treg differentiation in experimental autoimmune encephalomyelitis

Wan, C;Ping, CY;Shang, XY;Tian, JT;Zhao, SH;Li, L;Fang, SH;Sun, W;Zhao, YF;Li, ZY;Xu, YW;Mu, LL;Wang, JH;Kong, QF;Wang, GY;Li, HL;Sun, B;

MicroRNA 182 has been found to have a distinct contribution in the clonal expansion of activated- and functioning of specialized-helper T cells. In this study we knocked down microRNA 182 in vivo and induced experimental autoimmune encephalomyelitis (EAE) to determine the influences of microRNA 182 in the Treg cells functional specialization through Foxo1 dependent pathway in the peripheral lymphoid organs. Down-regulation of microRNA 182 significantly increased the proportions of Foxp3(+) T cells in the peripheral lymph nodes and spleen. In vivo study verified a positive correlation between microRNA 182 levels and symptom severity of EAE, and a negative correlation between microRNA 182 and the transcriptional factor Foxp3. In vitro polarization study also confirmed the contribution of Foxo1 in microRNA 182 mediated down-regulation of Foxp3(+) T cells. Together, our results provide evidence that during the development of EAE, microRNA 182 repressed Treg cells differentiation through the Foxo1 dependent pathway.