Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5.
The regulation of macrophage orientation pathological conditions is important but still incompletely understood. Here, we show that IL-10 and Rag1 double knockout mice spontaneously develop colitis with dominant M1 macrophage phenotype, suggesting that IL-10 regulates macrophage orientation in inflammation. We demonstrate that IL-10 stimulation induced miR-146b expression, and that the expression of miR-146b was impaired in IL-10 deficient macrophages. Our data show that miR-146b targets IRF5, resulting in the regulation of macrophage activation. Furthermore, miR-146b deficient mice developed intestinal inflammation with enhanced M1 macrophage polarization. Finally, miR-146b mimic treatment significantly suppresses M1 macrophage activation and ameliorates colitis development in vivo. Collectively, the results suggest that IL-10 dependent miR-146b plays an important role in the modulation of M1 macrophage orientation.
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Liang
L
Peng
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Hui
H
Zhang
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Yuanyuan
Y
Hao
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Feihong
F
Xu
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Jianjun
J
Yang
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Ruihua
R
Zhang
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Geming
G
Lu
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Zihan
Z
Zheng
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Miao
M
Cui
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
Chen-Feng
CF
Qi
Department of Biological Sciences, Center for Inflammation, Virginia Tech, Blacksburg, VA 24061, United States.
Chun
C
Chen
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Juan
J
Wang
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Yuan
Y
Hu
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States.
Di
D
Wang
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
Susan
S
Pierce
Department of Biological Sciences, Center for Inflammation, Virginia Tech, Blacksburg, VA 24061, United States.
Liwu
L
Li
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai,New York, NY 10029, United States; Institute of Immunology and Molecular Medicine, Jining Medical College, Jining, Shangdong 272067, China. Electronic address: Huabao.Xiong@mssm.edu.
Huabao
H
Xiong
D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D050835:Interferon Regulatory Factors; C498178:Irf5 protein, mouse; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse
CRISPR/Cas9; Colitis; Interleukin 10; Macrophage; miR-146b