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.
['Peng|Liang|L|', 'Zhang|Hui|H|', 'Hao|Yuanyuan|Y|', 'Xu|Feihong|F|', 'Yang|Jianjun|J|', 'Zhang|Ruihua|R|', 'Lu|Geming|G|', 'Zheng|Zihan|Z|', 'Cui|Miao|M|', 'Qi|Chen-Feng|CF|', 'Chen|Chun|C|', 'Wang|Juan|J|', 'Hu|Yuan|Y|', 'Wang|Di|D|', 'Pierce|Susan|S|', 'Li|Liwu|L|', 'Xiong|Huabao|H|']
D000818:Animals D065150:Cellular Reprogramming D016207:Cytokines D005786:Gene Expression Regulation D050835:Interferon Regulatory Factors D008262:Macrophage Activation D008264:Macrophages D051379:Mice D018345:Mice, Knockout D035683:MicroRNAs D034622:RNA Interference D016176:T-Lymphocyte Subsets
Macrophage Colitis miR-146b CRISPR/Cas9 Interleukin 10