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MicroRNA-425 facilitates pathogenic Th17 cell differentiation by targeting forkhead box O1 (Foxo1) and is associated with inflammatory bowel disease.
- Source :
-
Biochemical & Biophysical Research Communications . Feb2018, Vol. 496 Issue 2, p352-358. 7p. - Publication Year :
- 2018
-
Abstract
- Abstract 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. Highlights • MiR-425 expression is significantly increased in patients with IBD. • MiR-425 promotes pathogenic Th17 cell differentiation. • Foxo1 is a novel target of miR-425. • In vivo inhibition of miR-425 alleviates TNBS-induced colitis in mice. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 496
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 133765735
- Full Text :
- https://doi.org/10.1016/j.bbrc.2018.01.055