title: Downregulation of microRNA-107 in intestinal CD11c(+) myeloid cells in response to microbiota and proinflammatory cytokines increases IL-23p19 expression.
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.
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX, USA; Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Cao
authors.forename: Xiaocang
authors.initials: X
authors.lastname: Cao
authors.forename: Suxia
authors.initials: S
authors.lastname: Yao
authors.forename: Eric D
authors.initials: ED
authors.lastname: Carlsen
authors.forename: Lynn
authors.initials: L
authors.lastname: Soong
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Xiuping
authors.initials: X
authors.lastname: Liu
authors.forename: Zhanju
authors.initials: Z
authors.lastname: Liu
authors.forename: L Wayne
authors.initials: LW
authors.lastname: Duck
authors.forename: Charles O
authors.initials: CO
authors.lastname: Elson
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Cong
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology / Q000378:metabolism; D020029:Base Pairing; D001483:Base Sequence; D003092:Colitis / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D053760:Interleukin-23 Subunit p19 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008024:Ligands; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D064307:Microbiota; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053760:Interleukin-23 Subunit p19; D008024:Ligands; C555365:MIRN107 microRNA, mouse; D035683:MicroRNAs; D051193:Toll-Like Receptors
keywords: IL-23p19; Inflammatory bowel disease; MicroRNAs; TLR; miR-107