MiR155-deficient alleviated intestinal inflammation by downregualting the development and function of CD103+CD11b+DC in the lamina propria of intestine

Abstract

Abstract Inflammatory bowel disease (IBD) refers to inflammatory disorders of the gut with unclear pathogenesis. miR155 expression was increased in IBDs by upregulated Th1/Th17 cell response and proinflammatory factors to promote intestinal inflammation. Dendritic cell (DC) is a heterogeneous subsets in the intestine, and plays important roles in maintaining intestinal homeostasis. However, it is unclear whether miR155 regulate the differentiation and function of intestinal DC subsets to orchestrate inflammation in the intestinal microenvironment. Here, we found defiency of miR155 led to a significantly decreased number of CD103+CD11b+DC in the lamina propria (LP) of intestine at steady state, moreover, the yield of bone marrow-derived CD103+CD11b+DC induced by GM-CSF and Flt3L in vitro was also decreased compared to that of wild type (WT) mice. Further study showed that differency of miR155 had no effect on turnover rate and migration. Interestingly, we found the percentage and number of pre-cDC1 (CD103+DC precursor) in the BM were reduced significantly in the bone marrow of miR155-deficient mice compared to that of WT mice, and the transcriptor IRF4 and Notch2 expression of CD103+CD11b+DC in the LP was also decreased in miR155-deficient mice. In addition, CD103+DC and CD103+CD11b+DC in the LP of miR155-deficient mice exhibited a poor pro-inflammatory phenotype. Taken together, our results identifies a role of miR155 as a critical regular of intestinal homeostasis, which will be helpful for seeking a potential therapeutic target for the treatment of IBD.