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 infla...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161420/
https://www.ncbi.nlm.nih.gov/pubmed/27825654
http://dx.doi.org/10.1016/j.ebiom.2016.10.041
Descripción
Sumario: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.

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