MicroRNA-10a Negatively Regulates CD4+ T Cell IL-10 Production through Suppression of Blimp1
Wenjing Yang, Liang Chen, Leiqi Xu, Anthony J. Bilotta, Suxia Yao, Zhanju Liu, Yingzi Cong
Abstract
Abstract An uncontrolled CD4+ T cell response is a critical hallmark of autoimmune diseases. IL-10, which can be produced by both effector and regulatory CD4+ T cells, plays an essential role in the inhibition of autoimmunity. MicroRNAs are key molecules involved in regulating immune responses. However, how miR-10a regulates CD4+ T cell function in the pathogenesis of intestinal immune responses is not fully understood. In this study, we show that the mice with deficient miR-10a in CD4+ T cells were more resistant to intestinal inflammation upon inflammatory insult. miR-10a–deficient CD4+CD45Rbhi T cells were less colitogenic in Rag−/− mice, in which CD4+ T cell production of IL-10 was increased. miR-10a–deficient CD4+ T cells expressed a higher expression of IL-10 in vitro. Blocking the IL-10/IL-10R pathway in vivo aggravated colitis induced by miR-10a–deficient CD4+CD45Rbhi T cells. Mechanically, miR-10a suppressed CD4+ T cell production of IL-10 through targeting Prdm1, which encodes Blimp1. We further show that that CD4+ T cells lacking Blimp1 produced lower levels of IL-10 and induced more severe colitis in Rag−/− mice. These data thus establish the role of miR-10a in the inhibition of IL-10 production in CD4+ T cells to regulate intestinal homeostasis.