Institute of Health Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences and Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
Immunity. 2011 Aug 26;35(2):273-84. doi: 10.1016/j.immuni.2011.06.011. Epub 2011 Aug 11.
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.
神经祖细胞（NPC）治疗被认为是治疗多发性硬化症（MS）的一种有前途的治疗方式，可能通过神经修复发挥作用。在这里，我们表明，NPC 的静脉内给药通过选择性抑制致病性辅助性 T 细胞 17（Th17）细胞分化来改善实验性自身免疫性脑脊髓炎（EAE）。NPC 产生的白血病抑制因子（LIF）是观察到的 EAE 抑制的原因。通过诱导性 LIF 受体表达，LIF 抑制了 EAE 小鼠和 MS 患者中 Th17 细胞的分化。在分子水平上，LIF 通过触发激活细胞外信号调节激酶（ERK）和上调细胞因子信号转导抑制因子 3（SOCS3）表达的信号级联反应，对白细胞介素 6（IL-6）诱导的转录激活子 3（STAT3）磷酸化所需的 Th17 细胞分化产生拮抗作用。这项研究揭示了 LIF 在调节 Th17 细胞分化中的关键作用，并为 NPC 治疗 MS 的作用机制提供了深入了解。
