Oncotarget

Research Papers:

miR-21 silencing ameliorates experimental autoimmune encephalomyelitis by promoting the differentiation of IL-10-producing B cells

Hui Wang, Wenrong Xu, Qixiang Shao _ and Qing Ding

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Oncotarget. 2017; 8:94069-94079. https://doi.org/10.18632/oncotarget.21578

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Abstract

Hui Wang1, Wenrong Xu2, Qixiang Shao1 and Qing Ding1

1Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China

2Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China

Correspondence to:

Qixiang Shao, email: shao_qx@ujs.edu.cn

Qing Ding, email: qing_ding69@163.com

Keywords: microRNA-21, interleukin-10, regulatory B cells, experimental autoimmune encephalomyelitis

Received: June 29, 2017     Accepted: September 18, 2017     Published: October 06, 2017

ABSTRACT

IL-10-producing regulatory B (IL-10+ Breg) cells promote tolerance in autoimmune diseases and transplantation. However, it remains unclear whether microRNAs are involved in the development of IL-10+ Breg cells. Here, we found that microRNA-21 (miR-21) acts as an upstream regulator of IL-10 by targeting the 3' untranslated region of IL-10 mRNA. We also demonstrated that IL-10+ Breg cells exhibit lower miR-21 expression than non-Breg cells and that miR-21 acts as a potent negative regulator of the differentiation of IL-10+ Breg cells. Accordingly, specific inhibition of miR-21 using antisense oligonucleotides markedly promoted B cell IL-10 expression. Thus, IL-10 is a direct target of miR-21. Moreover, silencing of miR-21 significantly alleviated the severity of experimental autoimmune encephalomyelitis (EAE), and this change was associated with an increase in the number of IL-10+ Breg cells. Finally, we demonstrated that miR-21-silenced B cells exert their suppressive activity through effector T cells in an IL-10-dependent manner.

Thus, we characterized a B cell-intrinsic microRNA pathway that inhibits the differentiation of IL-10+ Breg cells and promotes autoimmunity. miR-21 silencing therefore represents a new therapeutic strategy for the treatment of autoimmune diseases.


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