Metformin inhibits the pathogenic functions of AChR-specific B and Th17 cells by targeting miR-146a

作者：Hao, Yue; Zhao, Wei; Chang, Lulu; Chen, Xingfan; Liu, Chonghui; Liu, Yang; Hou, Lixuan; Su, Yinchun; Xu, Hao; Guo, Yu; Sun, Qixu; Mu, Lili; Wang, Jinghua; Li, Hulun; Han, Junwei^*; Kong, Qingfei^*

来源：Immunology Letters, 2022, 250: 29-40.

DOI：10.1016/j.imlet.2022.09.002

• miR-146a
• EAMG
• T cells
• B cells
• Metformin

Myasthenia gravis (MG) is characterized by fatigable skeletal muscle weakness with a fluctuating and unpre-dictable disease course and is caused by circulating autoantibodies and pathological T helper cells. Regulation of B-cell function and the T-cell network may be a potential therapeutic strategy for MG. MicroRNAs (miRNAs) have emerged as potential biomarkers in immune disorders due to their critical roles in various immune cells and multiple inflammatory diseases. Aberrant miR-146a signal activation has been reported in autoimmune diseases, but a detailed exploration of the relationship between miR-146a and MG is still necessary. Using an experimental autoimmune myasthenia gravis (EAMG) rat model, we observed that miR-146a was highly expressed in the spleen but expressed at low levels in the thymus and lymph nodes in EAMG rats. Additionally, miR-146a expression in T and B cells was also quite different. EAMG-specific Th17 and Treg cells had lower miR-146a levels, while EAMG-specific B cells had higher miR-146a levels, indicating that targeted intervention against miR-146a might have diametrically opposite effects. Metformin, a drug that was recently demonstrated to alleviate EAMG, may rescue the functions of both Th17 cells and B cells by reversing the expression of miR-146a. We also investigated the downstream target genes of miR-146a in both T and B cells using bioinformatics screening and qPCR. Taken together, our study identifies a complex role of miR-146a in the EAMG rat model, suggesting that more caution should be paid in targeting miR-146a for the treatment of MG.

• 单位
  哈尔滨医科大学