MicroRNA-10a regulates intestinal mucosal dendritic cell development and function by targeting CD11c

Abstract

Abstract We have previously demonstrated that microRNA-10a (miR-10a), highly expressed in intestine DC and epithelial cells, and negatively regulated by microbiota, regulated T cell function and pathogenesis of inflammatory bowel diseases by targeting IL-12p40. However, whether and how miR-10a regulates mucosal DC development and function are largely unknown. In the present study, we found that intestinal lamina propria (LP) DC expressed higher levels of miR10a than that in mesenteric lymph node (MLN) and spleen DC. Retinoic acid (RA), a metabolite of Vitamin A (VitA), has been implicated in regulation of mucosal DC development. Interestingly, expression of ALDH1a, a gene encoding an enzyme converting VitA to RA, was positively associated with miR-10a expression in DC from LPDC, MLN DC and splenic DC. Treatment with RA up-regulated DC expression of miR-10a in vitro. Feeding mice diets with high levels of VitA (VAH) promoted, while feeding VitA deficient diets (VAD) decreased, LPDC expression of miR-10a. By using the luciferase assay, we identified CD11c as a target of miR-10a. In DC specific miR-10a deficient (CD11cCre miR10afl/fl, cKO) mice, CD11c+ DC, especially CD11c+CD11b+ DC, were significantly decreased in intestinal LP. When coculture with microbiota antigen specific T cells, cKO DC promoted the differentiation of T cell to IFNg+ Th1 cells but inhibited Foxp3+ Treg cell development. Collectively, our data demonstrated that miR-10a regulates mucosal DC development by targeting CD11c, and DC expression of miR-10a differentially regulates Th1 and Treg cell differentiation.