Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
Mol Cell Neurosci. 2013 Sep;56:85-95. doi: 10.1016/j.mcn.2013.03.005. Epub 2013 Mar 27.
Conventional therapies for autoimmune diseases produce nonspecific immune suppression, which are usually continued lifelong to maintain disease control, and associated with a variety of adverse effects. In this study, we found that spleen-derived dendritic cells (DCs) from the ongoing experimental autoimmune myasthenia gravis (EAMG) rats can be induced into tolerogenic DCs by atorvastatin in vitro. Administration of these tolerogenic DCs to EAMG rats on days 5 and 13 post immunization (p.i.) resulted in improved clinical symptoms, which were associated with increased numbers of CD4(+)CD25(+) T regulatory (Treg) cells and Foxp3 expression, decreased lymphocyte proliferation among lymph node mononuclear cells (MNC), shifted cytokine profile from Th1/Th17 to Th2 type cytokines, decreased level of anti-R97-116 peptide (region 97-116 of the rat acetylcholine receptor α subunit) IgG antibody in serum. These tolerogenic DCs can migrate to spleen, thymus, popliteal and inguinal lymph nodes after they were injected into the EAMG rats intraperitoneally. Furthermore, these tolerogenic DCs played their immunomodulatory effects in vivo mainly by decreased expression of CD86 and MHC class II on endogenous DCs. All these data provided us a new strategy to treat EAMG and even human myasthenia gravis (MG).
传统的自身免疫性疾病治疗方法产生非特异性免疫抑制，通常需要终身持续治疗以维持疾病控制，并且会伴随各种不良反应。在这项研究中，我们发现，正在进行的实验性自身免疫性重症肌无力（EAMG）大鼠的脾源性树突状细胞（DCs）可以在体外被阿托伐他汀诱导为耐受性 DCs。在免疫后第 5 天和第 13 天给 EAMG 大鼠给予这些耐受性 DCs，可改善临床症状，这与 CD4+CD25+T 调节（Treg）细胞和 Foxp3 表达增加、淋巴结单核细胞（MNC）中淋巴细胞增殖减少、细胞因子谱从 Th1/Th17 向 Th2 型细胞因子转变、血清中抗 R97-116 肽（大鼠乙酰胆碱受体α亚单位 97-116 区域）IgG 抗体水平降低有关。这些耐受性 DCs 可以在注射到 EAMG 大鼠腹腔内后迁移到脾脏、胸腺、腘窝和腹股沟淋巴结。此外，这些耐受性 DCs 主要通过降低内源性 DCs 表面 CD86 和 MHC Ⅱ类的表达在体内发挥其免疫调节作用。所有这些数据为我们提供了一种治疗 EAMG 甚至人类重症肌无力（MG）的新策略。
