title: MicroRNA-223 Regulates the Differentiation and Function of Intestinal Dendritic Cells and Macrophages by Targeting C/EBPβ.
abstract: Dendritic cells (DCs) and macrophages play important roles in maintaining intestinal homeostasis. However, the molecular mechanisms that regulate the differentiation and responses of intestinal DCs and macrophages remain poorly understood. Here, we have identified microRNA miR-223 as a key molecule for regulating these processes. Deficiency of miR-223 led to a significantly decreased number of intestinal CX3CR1(hi) macrophages at steady state. Both intestinal CX3CR1(hi) macrophages and CD103(+) conventional DCs (cDCs) in miR-223-deficient mice exhibited a strong pro-inflammatory phenotype. Moreover, miR-223-deficient monocytes gave rise to more monocyte-derived DCs (moDCs) and produced more pro-inflammatory cytokines upon stimulation. Using a mouse model of colitis, we demonstrated that the miR-223 deficiency resulted in more severe colitis. Target gene analysis further identified that the effects of miR-223 on DCs and macrophages were mediated by directly targeting C/EBPβ. Taken together, our study identifies a role for miR-223 as a critical regulator of intestinal homeostasis.
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Chunxi
authors.initials: C
authors.lastname: Liu
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University School of Medicine, Beijing 100084, China. Electronic address: wuli@tsinghua.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics* / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation; D002478:Cells, Cultured; D003092:Colitis / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D000073883:CX3C Chemokine Receptor 1; C545013:Cebpb protein, mouse; C471885:Cx3cr1 protein, mouse; C544877:MIRN223 microRNA, mouse; D035683:MicroRNAs; D019707:Receptors, Chemokine