Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha, China.
Department of Neurology, The First Hospital in Changsha City, Changsha, China.
Inflammation. 2017 Aug;40(4):1460-1473. doi: 10.1007/s10753-017-0589-2.
Myasthenia gravis (MG) is a neurological autoimmune disease characterized by fluctuating weakness of certain voluntary muscles. Current treatments for MG are largely directed at suppressing the whole immune system by using immunosuppressants or glucocorticoids and often cause several side effects. The ideal therapeutic methods for MG should suppress aberrant immunoactivation specifically, while retaining normal function of the immune system. In this study, we first produced exosomes from microRNA-146a overexpressing dendritic cells (DCs). Then, we observed suppressive effects of those exosomes in experimental autoimmune myasthenia gravis (EAMG) mice. Results showed that exosomes from microRNA-146a overexpressing DCs expressed decreased levels of CD80 and CD86. In experimental autoimmune MG, exosomes from microRNA-146a overexpressing DCs suppressed ongoing clinical MG in mice and altered T helper cell profiles from Th1/Th17 to Th2/Treg both in serum and spleen, and the therapeutic effects of those exosomes were antigen-specific and partly dose dependent. All the findings provide experimental basis for antigen-specific therapy of MG.
重症肌无力（MG）是一种以某些随意肌波动性无力为特征的神经自身免疫性疾病。目前针对 MG 的治疗方法主要是通过使用免疫抑制剂或糖皮质激素来抑制整个免疫系统，常常会引起多种副作用。MG 的理想治疗方法应该是特异性抑制异常免疫激活，同时保留免疫系统的正常功能。在这项研究中，我们首先从过表达 microRNA-146a 的树突状细胞（DC）中产生外泌体。然后，我们观察了这些外泌体在实验性自身免疫性重症肌无力（EAMG）小鼠中的抑制作用。结果表明，过表达 microRNA-146a 的 DC 产生的外泌体表达的 CD80 和 CD86 水平降低。在实验性自身免疫性 MG 中，过表达 microRNA-146a 的 DC 产生的外泌体抑制了小鼠正在进行的临床 MG，并改变了血清和脾脏中 Th1/Th17 向 Th2/Treg 的 T 辅助细胞谱，这些外泌体的治疗效果具有抗原特异性且部分依赖于剂量。所有这些发现为 MG 的抗原特异性治疗提供了实验基础。
