• Lianhua Yan, Fen Hu, Xiaofei Yan, Yuzhen Wei, Wenhan Ma, Ya Wang, Shuai Lu, and Zhaohui Wang.
• Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tong Ji Medical College of Huahzong University of Science and Technology, 1277 Jiefang Ave, Wuhan, 430022, China.
• J. Mol. Med. 2016 Sep 1; 94 (9): 1063-79.

UnlabelledExperimental autoimmune myocarditis (EAM) is an inflammatory cardiac disease driven by autoantigen-specific CD4+ T cells. Th17 and Treg cells are crucial participants in immune response. A wide variety of immune disorders are associated with Th17/Treg imbalance. MicroRNA-155 (miR-155) is a pivotal regulator of the immune system. However, the modulatory effect of miR-155 on Th17/Treg immune response during EAM is unknown. Our study aims to investigate the potential role of miR-155 on the development of autoimmune myocarditis. In this study, we revealed that miR-155 expression was highly elevated in heart tissue and CD4+ T cells during EAM. Also, we identified a proliferative and functional imbalance of Th17/Treg in EAM, which is due to a more active development of Th17 cells and an increased resistance of Th17 cells to Treg-mediated suppression. MiR-155 inhibition in EAM resulted in attenuated severity of disease and cardiac injury, reduced Th17 immune response, and decreased dendritic cell (DC) function of secreting Th17-polarizing cytokines. Furthermore, CD4+ T cells from miR-155-inhibited EAM mice exhibited reduced proliferation and IL-17A secretion in response to autoantigen. Finally, we confirmed an indispensable positive role of miR-155 on the differentiation of Th17 cells and the DC function of secreting Th17-polarizing cytokines through in vitro studies. These findings demonstrated that miR-155 adversely promotes EAM by driving a Th17/Treg imbalance in favor of Th17 cells, and anti-miR-155 treatment can significantly reduce the autoimmune response thus to ameliorate EAM, suggesting that miR-155 inhibition could be a promising therapeutic strategy for the treatment of autoimmune myocarditis.Key MessageMiR-155 expression was highly elevated in EAM mice. An imbalance of Th17/Treg existed in EAM mice. MiR-155 inhibition in EAM attenuated disease severity and cardiac injury. MiR-155 inhibition suppressed Th17 immune response in EAM. MiR-155 inhibition reduced DC function of secreting Th17-polarizing cytokines in EAM.

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