miR-10a inhibits dendritic cell activation and Th1/Th17 cell immune responses in IBD

Wei Wu, Chong He, Changqin Liu, Anthony T. Cao, Xiaochang Xue, Heather L. Evans-Marin, Mingming Sun, Leilei Fang, Suxia Yao, Irina V. Pinchuk, Don W. Powell, Zhanju Liu, Yingzi Cong

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66 Scopus citations

Abstract

Objective: Although both innate and adaptive responses to microbiota have been implicated in the pathogenesis of IBD, it is still largely unknown how they are regulated during intestinal inflammation. In this report, we investigated the role of microRNA (miR)-10a, a small, non-coding RNA, in the regulation of innate and adaptive responses to microbiota in IBD. Methods: miR-10a expression was analysed in the inflamed mucosa of IBD patients treated with or without antitumour necrosis factor (anti-TNF) monoclonal antibodies (mAb) (infliximab) by qRT-PCR. Human monocyte-derived dendritic cells (DC) and IBD CD4+ T cells were transfected with miR-10a precursor to define their effect on the function of DC and CD4+ T cells. Results: The expression of miR-10a was markedly decreased, while NOD2 and interleukin (IL)-12/IL-23p40 were significantly increased, in the inflamed mucosa of IBD patients compared with those in healthy controls. Commensal bacteria, TNF and interferon-γ inhibited human DC miR-10a expression in vitro. Anti-TNF mAb treatment significantly promoted miR-10a expression, whereas it markedly inhibited NOD2 and IL-12/IL-23p40 in the inflamed mucosa. We further identified NOD2, in addition to IL-12/IL-23p40, as a target of miR-10a. The ectopic expression of the miR-10a precursor inhibited IL-12/IL-23p40 and NOD2 in DC. Moreover, miR-10a was found to markedly suppress IBD T helper (Th)1 and Th17 cell responses. Conclusions: Our data indicate that miR-10a is decreased in the inflamed mucosa of IBD and downregulates mucosal inflammatory response through inhibition of IL-12/IL-23p40 and NOD2 expression, and blockade of Th1/Th17 cell immune responses. Thus, miR-10a could play a role in the pathogenesis and progression of IBD.

Original languageEnglish (US)
Pages (from-to)1755-1764
Number of pages10
JournalGut
Volume64
Issue number11
DOIs
StatePublished - Nov 2015

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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    Wu, W., He, C., Liu, C., Cao, A. T., Xue, X., Evans-Marin, H. L., Sun, M., Fang, L., Yao, S., Pinchuk, I. V., Powell, D. W., Liu, Z., & Cong, Y. (2015). miR-10a inhibits dendritic cell activation and Th1/Th17 cell immune responses in IBD. Gut, 64(11), 1755-1764. https://doi.org/10.1136/gutjnl-2014-307980