Inhibition of microRNA-155 ameliorates experimental autoimmune myocarditis by modulating Th17/Treg immune response

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.