来自中科院上海生命科学研究院/上海交大医学院健康科学研究所的研究人员获得了多发性硬化疾病免疫调节机制研究的新进展，深入探讨了胚胎干细胞来源的神经前体细胞（NPC）在人类多发性硬化症（Multiple Sclerosis）的小鼠模型——实验性自身免疫性脑脊髓炎（EAE）中的治疗效果及作用机制。这一研究成果公布在Immunity杂志上，并被Nature China作为亮点推荐。
多发性硬化是以中枢神经系统白质脱髓鞘病变为特点的自身免疫病。流行病学显示该病全球的患者超过100万例，我国约有6.5万例。迄今为止，该病发病机制仍不明确，对症治疗仍是临床上亟待解决的难题。神经干细胞具有自我更新和多向分化潜能，可以修复和替代病变的神经细胞，为治疗人类多发性硬化症、帕金森病、阿尔兹海默病等神经系统退行性疾病带来了新的希望。
曹巍、杨益清及王正毅三位博士研究生在臧敬五研究员的指导下，选择目前国际公认的MS的理想小鼠EAE模型进行实验，经过大量研究发现，NPC细胞通过外周免疫调节作用显著地缓解了EAE，这种作用是由NPC细胞分泌的神经营养因子——白血病抑制因子（Leukemia inhibitory factor, LIF）选择性抑制致病性Th17细胞的分化所介导的。
进一步研究表明，LIF与其受体结合后，激活细胞外信号调节MAP激酶（extracellular signal-regulated MAP kinase，ERK）的磷酸化进而上调细胞因子信号传导负调控因子3（suppressor of cytokine signaling 3，SOCS3）的表达水平，最终抑制Th17细胞分化过程中关键的转录因子信号传导子及转录激活子3（signal transducer and activator of transcription 3，STAT3）的磷酸化。
这一研究深入探究了NPC在MS治疗中的作用机制并揭示了LIF在免疫调节方面发挥的关键作用。该项成果为进一步研究神经干细胞在治疗人类多发性硬化症中的重要作用提供了重要的实验资料。
相关英文论文摘要：
Leukemia Inhibitory Factor Inhibits T Helper 17 Cell Differentiation and Confers Treatment Effects of Neural Progenitor Cell Therapy in Autoimmune Disease
Neural progenitor cell (NPC) therapy is considered a promising treatment modality for multiple sclerosis (MS), potentially acting through neural repair. Here, we showed that intravenous administration of NPCs ameliorated experimental autoimmune encephalomyelitis (EAE) by selectively inhibiting pathogenic T helper 17 (Th17) cell differentiation. Leukemia inhibitory factor (LIF) produced by NPCs was responsible for the observed EAE suppression. Through the inducible LIF receptor expression, LIF inhibited the differentiation of Th17 cells in EAE mice and that from MS subjects. At the molecular level, LIF exerted an opposing effect on interleukin 6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation required for Th17 cell differentiation by triggering a signaling cascade that activated extracellular signal-regulated MAP kinase (ERK) and upregulated suppressor of cytokine signaling 3 (SOCS3) expression. This study reveals a critical role for LIF in regulating Th17 cell differentiation and provides insights into the mechanisms of action of NPC therapy in MS.
英文论文链接：https://www.sciencedirect.com/science/article/pii/S1074761311003025
