MicroRNA-10a Negatively Regulates CD4⁺ T Cell IL-10 Production through Suppression of Blimp1.

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⁺CD45Rb^hi 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⁺CD45Rb^hi 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.

SUBMITTER: Yang W 

PROVIDER: S-EPMC8323958 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature