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miR-10a inhibits dendritic cell activation and Th1/Th17 cell immune responses in IBD
  1. Wei Wu1,2,
  2. Chong He1,2,
  3. Changqin Liu1,
  4. Anthony T Cao2,
  5. Xiaochang Xue2,
  6. Heather L Evans-Marin2,
  7. Mingming Sun1,
  8. Leilei Fang1,
  9. Suxia Yao2,
  10. Irina V Pinchuk3,
  11. Don W Powell3,
  12. Zhanju Liu1,
  13. Yingzi Cong2,4
  1. 1Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
  2. 2Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA
  3. 3Department of Medicine, The University of Texas Medical Branch, Galveston, Texas, USA
  4. 4Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA
  1. Correspondence to Dr Zhanju Liu, Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China; liuzhanju88@126.com; and Dr Yingzi Cong, Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA; yicong{at}utmb.edu

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.

  • IBD BASIC RESEARCH
  • DENDRITIC CELLS
  • T LYMPHOCYTES
  • MUCOSAL IMMUNITY
  • CYTOKINES

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