Downregulation of microRNA-107 in intestinal CD11c+ myeloid cells in response to microbiota and proinflammatory cytokines increases IL-23p19 expression

Academic Article

Abstract

  • Commensal flora plays an important role in the development of the mucosal immune system and in maintaining intestinal homeostasis. However, the mechanisms involved in regulation of host-microbiota interaction are still not completely understood. In this study, we examined how microbiota and intestinal inflammatory conditions regulate host microRNA expression and observed lower microRNA-107 (miR-107) expression in the inflamed intestines of colitic mice, compared with that in normal control mice. miR-107 was predominantly reduced in epithelial cells and CD11c+ myeloid cells including dendritic cells and macrophages in the inflamed intestines. We demonstrate that IL-6, IFN-γ, and TNF-α downregulated, whereas TGF-β promoted, miR-107 expression. In addition, miR-107 expression was higher in the intestines of germ-free mice than in mice housed under specific pathogen-free conditions, and the presence of microbiota downregulated miR-107 expression in DCs and macrophages in a MyD88- and NF-κB-dependent manner. We determined that the ectopic expression of miR-107 specifically repressed the expression of IL-23p19, a key molecule in innate immune responses to commensal bacteria. We concluded that regulation of miR-107 by intestinal microbiota and proinflammatory cytokine serve as an important pathway for maintaining intestinal homeostasis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Xue X; Cao AT; Cao X; Yao S; Carlsen ED; Soong L; Liu CG; Liu X; Liu Z; Duck LW
  • Start Page

  • 673
  • End Page

  • 682
  • Volume

  • 44
  • Issue

  • 3