title: Inhibition of microRNA-155 ameliorates experimental autoimmune myocarditis by modulating Th17/Treg immune response.
abstract: Experimental 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.
  
  
  
  MiR-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.
authors.affiliation: 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.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Yan
authors.affiliation: 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.
authors.forename: Fen
authors.initials: F
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yan
authors.affiliation: 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.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Shuai
authors.initials: S
authors.lastname: Lu
authors.affiliation: 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. wuxiaohongtian@163.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity / Q000235:genetics; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D007150:Immunohistochemistry; D056747:Immunomodulation; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009205:Myocarditis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse
keywords: Autoimmune myocarditis; Dendritic cell; MicroRNA-155; Th17; Treg