State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
Int Immunopharmacol. 2012 Oct;14(2):217-23. doi: 10.1016/j.intimp.2012.07.003. Epub 2012 Jul 24.
Myasthenia gravis (MG) is a T cell-dependent and B cell-mediated autoimmune disease of neuromuscular junctions and cytokines may play a crucial role in the pathogenesis and perpetuation of MG. MicroRNAs (miRNAs) have been implicated as fine-tuning regulators controlling diverse biological processes at the level of posttranscriptional repression. Dysregulation of miRNAs has been described in various disease states. In this study, miRNA microarrays identified let-7 family to be decreased in peripheral blood mononuclear cells (PBMCs) from MG patients compared to the healthy controls. We next demonstrated the differential expression of let-7 family in larger samples by quantitative real-time PCR. Using a combination of bioinformatics and molecular approaches, we confirmed IL-10 as a target for let-7c. IL-10 expression also showed a negative correlation with let-7c expression in PBMCs from MG patients. Further experiments revealed that induced levels of IL-10 were inversely related to let-7c levels. We also showed that let-7c could regulate IL-10 expression in Jurkat cells. In summary, our results suggest that abnormal expression/regulation of microRNAs may contribute to or be indicative of the initiation and progression of MG.
重症肌无力（MG）是一种 T 细胞依赖性和 B 细胞介导的自身免疫性疾病，作用于神经肌肉接头，细胞因子可能在 MG 的发病机制和持续中发挥关键作用。microRNAs（miRNAs）已被认为是精细调节因子，在转录后抑制水平上控制着各种生物学过程。miRNAs 的失调已在各种疾病状态中得到描述。在这项研究中，miRNA 微阵列确定与健康对照组相比，重症肌无力患者外周血单个核细胞（PBMCs）中的 let-7 家族减少。我们接下来通过定量实时 PCR 证明了较大样本中 let-7 家族的差异表达。通过生物信息学和分子方法的组合，我们证实 IL-10 是 let-7c 的靶标。重症肌无力患者 PBMCs 中的 IL-10 表达也与 let-7c 表达呈负相关。进一步的实验表明，诱导的 IL-10 水平与 let-7c 水平呈负相关。我们还表明，let-7c 可以调节 Jurkat 细胞中的 IL-10 表达。总之，我们的结果表明，miRNAs 的异常表达/调节可能导致或提示 MG 的发生和进展。
