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MicroRNA-425 facilitates pathogenic Th17 cell differentiation by targeting forkhead box O1 (Foxo1) and is associated with inflammatory bowel disease
- Yang, Xue, He, Qinyu, Guo, Zhenzhen, Xiong, Fei, Li, Yi, Pan, Yan, Gao, Caiping, Li, Liangping, He, Chong
- Biochemical and biophysical research communications 2018 v.496 no.2 pp. 352-358
- CD4-positive T-lymphocytes, autoimmune diseases, cell differentiation, colitis, disease severity, gain-of-function mutation, interleukin-17, mice, microRNA, mucosa, pathogenesis, patients, therapeutics
- Inflammatory bowel disease (IBD) is a chronic autoimmune disease, and its pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as a crucial regulator of autoimmune diseases. In this study, we demonstrated, for the first time, that miR-425 was significantly up-regulated in peripheral blood mononuclear cells (PBMC) and mucosa of patients with IBD. In note, T helper (Th) 17 cells were found to be the major source of miR-425 expression. Using gain-of-function approaches, we demonstrated that miR-425 could facilitate the differentiation of CD4+ T cells into Th17 lineage. In addition, forkhead box O1 (Foxo1) was identified as a novel target gene of miR-425, which was able to inhibit Th17 cell differentiation, and it was observed to be markedly decreased in PBMC and mucosa of patients with IBD. Notably, in vivo inhibition of miR-425 significantly alleviated the disease severity of TNBS-induced colitis in mice, with down-regulated levels of IL-17A. Our data reveal a novel mechanism in which the elevated miR-425 in IBD mediates pathogenic Th17 cell generation through down-regulation of Foxo1. In vivo blockade of miR-425 may serve as a novel therapeutic approach in the treatment of IBD.