title: miR-10a inhibits dendritic cell activation and Th1/Th17 cell immune responses in IBD.
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.
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Changqin
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Cao
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Evans-Marin
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Suxia
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Medicine, The University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Pinchuk
authors.affiliation: Department of Medicine, The University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Don W
authors.initials: DW
authors.lastname: Powell
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Zhanju
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Cong
mesh_terms: D000328:Adult; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: C547183:MIRN10 microRNA, human; D035683:MicroRNAs
keywords: CYTOKINES; DENDRITIC CELLS; IBD BASIC RESEARCH; MUCOSAL IMMUNITY; T LYMPHOCYTES