Original Research ARTICLE
Critical role of alternative M2 skewing in miR-155 deletion-mediated protection of colitis
- 1Army Medical University, China
- 2Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, China
Inflammatory bowel disease (IBD) is associated with dysregulation of both innate and adaptive immune response in the intestine. MiR-155 is often 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 sulphate sodium (DSS)-induced colitis 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 towards 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 towards 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.
Keywords: M2 macrophages, miR-155, Colitis, C/EBPβ, SOCS1
Received: 22 Nov 2017;
Accepted: 11 Apr 2018.
Edited by:Stipan Jonjic, University of Rijeka, Croatia
Reviewed by:Helder Nakaya, Universidade de São Paulo, Brazil
Hridayesh Prakash, All India Institute of Medical Sciences, India
Ludmila R. Ferreira, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil
Copyright: © 2018 Li, zhang, guo, yang, fan, ye, tian, yu, ai, shen, he, yan, li, luo, wu and li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Jintao Li, Army Medical University, Chongqing, China, firstname.lastname@example.org