Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5.
Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5.
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DOI：
10.1016/j.ebiom.2016.10.041
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发表时间：
2016-12
期刊：
影响因子：
11.1
通讯作者：
Xiong, Huabao
中科院分区：
文献类型：
--
作者：
Peng, Liang;Zhang, Hui;Hao, Yuanyuan;Xu, Feihong;Yang, Jianjun;Zhang, Ruihua;Lu, Geming;Zheng, Zihan;Cui, Miao;Qi, Chen-Feng;Chen, Chun;Wang, Juan;Hu, Yuan;Wang, Di;Pierce, Susan;Li, Liwu;Xiong, Huabao
巨噬细胞定位的病理状态的调节很重要，但仍不完全清楚。在这里，我们发现IL-10和Rag1双基因敲除小鼠自发地发展成以M1巨噬细胞表型为主的结肠炎，提示IL-10在炎症中调节巨噬细胞的方向。我们发现IL-10刺激诱导了miR-146b的表达，而在IL-10缺乏的巨噬细胞中miR-146b的表达受到了损害。我们的数据表明miR-146b靶向IRF5，导致调节巨噬细胞的激活。此外，miR-146b缺陷小鼠出现肠道炎症，M1巨噬细胞极化增强。最后，miR-146b模拟治疗显著抑制M1巨噬细胞的激活，并改善体内结肠炎的发展。综上所述，这些结果表明依赖于IL-10的miR-146b在调节M1巨噬细胞的定向方面起着重要作用。白介素10诱导的miR-146b通过靶向IRF5在巨噬细胞极化和结肠炎的发生发展中起关键作用。MiR-146b模拟治疗显著抑制M1巨噬细胞的激活并改善结肠炎的发展。白介素10和白介素受体明显参与炎症性肠病和其他炎症性疾病的发生发展。值得注意的是，白介素10和白介素10受体突变与炎症性肠病明显相关。在本研究中，我们证明了白介素10诱导的miR-146b通过靶向IRF5在巨噬细胞极化和结肠炎的发生发展中起关键作用。MiR-146b模拟治疗显著抑制M1巨噬细胞的激活并改善结肠炎的发展。这些结果突显了miR146b在控制免疫反应和炎症性疾病发病机制中的强大作用。
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. Interleukin 10-induced miR-146b plays a critical role in the regulation of macrophage polarization and colitis development by targeting IRF5. Treatment with miR-146b mimic significantly suppresses M1 macrophage activation and ameliorates colitis development. Interleukin 10 and Interleukin receptor are clearly involved in the development of inflammatory bowel diseases and other inflammatory diseases. Notably, the mutation of Interleukin 10 and Interleukin 10 receptor are clearly correlated with inflammatory bowel diseases. In the present study we show that Interleukin 10-induced miR-146b plays a critical role in the regulation of macrophage polarization and colitis development by targeting IRF5. Treatment with miR-146b mimic significantly suppresses M1 macrophage activation and ameliorates colitis development. The results highlight the potent role of miR146b in the control of immune responses and pathogenesis of inflammatory diseases.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
4.1
作者：
Ge Q;Brichard S;Yi X;Li Q
通讯作者：
Li Q
DOI：
10.1038/nri3494
发表时间：
2013-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
1.3
作者：
Mills, Charles D.
通讯作者：
Mills, Charles D.
影响因子：
82.9
作者：
Brown, Brian D.;Venneri, Mary Anna;Naldini, Luigi
通讯作者：
Naldini, Luigi