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P002. miR-10a suppresses dendrite cell activation and Th1/Th17 cell responses in inflammatory bowel disease

W. Wu, C. Liu, Z. Liu, Shanghai Tenth People's Hospital, Tongji University, Department of Gastroenterology, Shanghai, China

Background

Although both innate and adaptive responses to microbiota have been implicated in maintenance of intestinal homeostasis and pathogenesis of inflammatory bowel disease (IBD), it is still largely unknown how they are regulated during intestinal inflammation. In this report, we investigated the role of microRNA-10a (miR-10a), a small, evolutionarily conserved, non-coding RNA, in regulation of innate and adaptive responses to microbiota in IBD.

Methods

miR-10a expression was analyzed in the inflamed mucosa of IBD patients treated with or without anti-TNF mAb (infliximab) by qRT-PCR. Human monocyte-derived dendritic cells (DC) were transfected with miR-10a precursor and inhibitor to define its effect on DC cytokine expression. Further, the role of miR-10a in regulating IBD CD4+ T cell responses was investigated in vitro.

Results

The expression of miR-10a was found to be markedly decreased, while NOD2 and IL-12/IL-23p40 were significantly increased, in the inflamed mucosa of IBD patients compared to those in healthy controls. Anti-TNF mAb treatment significantly promoted miR-10a expression, whereas markedly inhibited NOD2 and IL-12/IL-23p40 in the inflamed mucosa of Crohn's disease (CD) patients. Commensal bacteria, TNF-α, and IFN-γ could inhibit human DC miR-10a expression in vitro. miR-10a was observed to downregulate DC expression of IL-12/IL-23p40 and NOD2, in that overexpression of miR-10a inhibited human DC IL-12/IL-23p40 and NOD2 expression and production of IL-12 and IL-23. Moreover, miR-10a was found to markedly suppress IBD Th1 and Th17, but not Th2, cell responses.

Conclusion

Our data indicate that miR-10a is decreased in the inflamed mucosa of IBD. Further, it downregulates mucosal inflammatory response through inhibition of IL-12/IL-23p40 and NOD2 expression, and blockade of Th1/Th17 cell responses. Thus, target therapy directed against miR-10a may represent a promising approach in the treatment of IBD.