%0 Figure %A Li, Jintao %A Zhang, Ji %A Guo, Hongxia %A Yang, Shimin %A Fan, Weiping %A Ye, Nan %A Tian, Zhiqiang %A Yu, Tiantian %A Ai, Guoping %A Shen, Zigang %A He, Haiyang %A Yan, Ping %A Lin, Hui %A Luo, Xue %A Li, Hongli %A Wu, Yuzhang %D 2020 %T Image_8_Critical Role of Alternative M2 Skewing in miR-155 Deletion-Mediated Protection of Colitis.tiff %U https://frontiersin.figshare.com/articles/figure/Image_8_Critical_Role_of_Alternative_M2_Skewing_in_miR-155_Deletion-Mediated_Protection_of_Colitis_tiff/11843109 %R 10.3389/fimmu.2018.00904.s012 %2 https://frontiersin.figshare.com/ndownloader/files/21704037 %K M2 macrophages %K miR-155 %K colitis %K C/EBPβ %K SOCS1 %X

Inflammatory bowel disease (IBD) is associated with dysregulation of both innate and adaptive immune response in the intestine. MicroRNA (miR)-155 is frequently expressed and functions in many immune cell types. Besides its function in adaptive immunity, miR-155 is a key regulator of the innate immune response in macrophages, dendritic cells, and even in epithelia cells. Although the roles of miR-155 within T and B lymphocytes in colitis have been reported, its function in innate immune cells has not been thoroughly examined. In this study, the dextran sulfate sodium (DSS)-induced colitis model was established in wild-type (WT) and miR-155−/− mice. Our results showed that miR-155 deficiency in macrophages recapitulated the alleviated colitis feature of miR-155−/− mice and appeared to skew toward the alterative M2 phenotype. Notably, the predominance of M2 in colon can result in dampened intestinal immune cell proliferation and inhibit CD4 T cell polarization toward Th1 and Th17. Moreover, C/EBPβ and SOCS1 were demonstrated as two key functional targets in this process. We also provided evidence for use of miR-155 inhibitor to treat colitis. Collectively, the findings highlight the central role of alternative M2 skewing for miR-155 function in colitis and reveal that macrophages might be a main target for therapeutics.

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