MiR-181a regulates CD4+ T cell activation and differentiation by targeting IL-2 in the pathogenesis of myasthenia gravis.

Recently, microRNAs (miRNAs) have been reported to play crucial roles in immune responses and other biological processes, but the role of miR-181a in myasthenia gravis (MG) has been relatively less studied. We found that miR-181a was downregulated in the peripheral blood mononuclear cells (PBMCs) of MG patients and was associated with QMGs and anti-AChR Ab levels. In vitro experiments indicated that miR-181a was involved in the modulation of CD4+ T cell activation and plasticity and that miR-181a decreased the expression level of the Th1-related transcription factor T-bet and the Th17-related transcription factor RORγt. In the in vivo experiment, miR-181a treatment alleviated experimental autoimmune myasthenia gravis (EAMG) symptoms and affected both CD4+ T cell differentiation and the production of anti-AChR antibodies. Moreover, in this study, we also found that IL-2 was regulated by miR-181a and that its expression level showed a strong negative correlation with miR-181a levels in MG patients. To illustrate that the expression levels of both IL-2 and miR-181a were sensitive to immunomodulatory therapy treatment in MG, we found that IL-2 and miR-181a were correlated with clinical severity. These findings demonstrate that miR-181a can contribute to the pathogenesis of MG by regulating IL-2 expression. This article is protected by copyright. All rights reserved.