Downregulation of microRNA-107 in intestinal CD11c(+) myeloid cells in response to microbiota and proinflammatory cytokines increases IL-23p19 expression.
Downregulation of microRNA-107 in intestinal CD11c(+) myeloid cells in response to microbiota and proinflammatory cytokines increases IL-23p19 expression.
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DOI：
10.1002/eji.201343717
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发表时间：
2014-03
影响因子：
5.4
通讯作者：
Cong, Yingzi
中科院分区：
文献类型：
--
作者：
Xue, Xiaochang;Cao, Anthony T;Cao, Xiaocang;Yao, Suxia;Carlsen, Eric D;Soong, Lynn;Liu, Chang-Gong;Liu, Xiuping;Liu, Zhanju;Duck, L Wayne;Elson, Charles O;Cong, Yingzi
共生菌群在粘膜免疫系统的发育和维持肠道稳态中起着重要的作用。然而，宿主-微生物群相互作用的调节机制仍未完全了解。在本研究中，我们研究了微生物群和肠道炎症如何调节宿主microRNA的表达，并观察到与正常对照小鼠相比，结肠炎小鼠炎症肠道中microRNA-107 （miR-107）的表达较低。炎症肠道上皮细胞和CD11c+髓细胞（包括树突状细胞和巨噬细胞）中miR-107主要减少。我们发现IL-6、IFN-γ和TNF-α下调，而TGF-β促进miR-107的表达。此外，miR-107在无菌小鼠肠道中的表达高于特定无病原体条件下的小鼠，微生物群的存在以MyD88-和NF-κ b依赖的方式下调了dc和巨噬细胞中miR-107的表达。我们确定miR-107的异位表达特异性抑制IL-23p19的表达，IL-23p19是对共生菌的先天免疫应答的关键分子。我们得出结论，肠道微生物群和促炎细胞因子对miR-107的调控是维持肠道稳态的重要途径。
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 pro-inflammatory cytokine serve as an important pathway for maintaining intestinal homeostasis.