Li Heng, Wang Cong-Cong, Zhang Min, Li Xiao-Li, Zhang Peng, Yue Long-Tao, Miao Shuai, Wang Shan, Liu Ying, Li Yan-Bin, Duan Rui-Sheng
Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
Mol Cell Neurosci. 2015 Sep;68:284-92. doi: 10.1016/j.mcn.2015.08.010. Epub 2015 Aug 24.
We previously demonstrated that atorvastatin induced immature dendritic cells (DCs) derived from spleen in vitro. Administration of these tolerogenic DCs led to amelioration of experimental autoimmune myasthenia gravis (EAMG). The protective effect was mainly mediated by inhibited cellular immune response, including up-regulated regulatory T cells and shifted Th1/Th17 to Th2 cytokines. The present study employed atorvastatin-modified bone marrow-derived DCs (AT-BMDCs) to explore the effect of tolerogenic DCs on humoral immune response of EAMG and further elucidate the underlying mechanisms. Our data showed that AT-BMDCs reduced the quantity and the relative affinity of pathogenic antibodies, suppressed germinal center response, decreased follicular helper T cells and IL-21, and increased regulatory B cells. These results suggest that AT-BMDCs ameliorate EAMG by regulating humoral immune response, thus providing new insights into therapeutic approaches of myasthenia gravis and other autoimmune diseases.
我们之前证明，阿托伐他汀在体外可诱导源自脾脏的未成熟树突状细胞（DCs）。给予这些具有耐受性的DCs可改善实验性自身免疫性重症肌无力（EAMG）。这种保护作用主要是通过抑制细胞免疫反应介导的，包括上调调节性T细胞以及将Th1/Th17细胞因子转变为Th2细胞因子。本研究采用阿托伐他汀修饰的骨髓源性DCs（AT-BMDCs）来探究具有耐受性的DCs对EAMG体液免疫反应的影响，并进一步阐明其潜在机制。我们的数据表明，AT-BMDCs可减少致病性抗体的数量和相对亲和力，抑制生发中心反应，减少滤泡辅助性T细胞和IL-21，并增加调节性B细胞。这些结果表明，AT-BMDCs通过调节体液免疫反应改善EAMG，从而为重症肌无力和其他自身免疫性疾病的治疗方法提供了新的见解。
