Leukemia Inhibitory Factor Inhibits T Helper 17 Cell Differentiation and Confers Treatment Effects of Neural Progenitor Cell Therapy in Autoimmune Disease
Leukemia Inhibitory Factor Inhibits T Helper 17 Cell Differentiation and Confers Treatment Effects of Neural Progenitor Cell Therapy in Autoimmune Disease
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DOI：
10.1016/j.immuni.2011.06.011
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发表时间：
2011-08-26
期刊：
影响因子：
32.4
通讯作者：
Zhang, Jingwu Z.
中科院分区：
文献类型：
--
作者：
Cao, Wei;Yang, Yiqing;Zhang, Jingwu Z.
神经前体细胞(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，我们发现静脉注射NP可通过选择性抑制致病T辅助17(Th17)细胞分化来改善实验性自身免疫性脑脊髓炎(EAE)。鼻咽癌细胞产生的白血病抑制因子(LIF)对EAE的抑制起作用。通过诱导LIE受体的表达，LIE抑制了EAE小鼠和MS患者Th17细胞的分化。在分子水平上，LIF通过激活细胞外信号调节的MAP激酶(ERK)和上调的细胞因子信号转导抑制因子3(SOCS3)的表达，对白介素6(IL-6)诱导的Th17细胞分化所需的信号转导和转录激活因子3(STAT3)的磷酸化起相反的作用。这项研究揭示了LIF在调节Th17细胞分化中的关键作用，并为鼻咽癌治疗MS的作用机制提供了见解。
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 LIE receptor expression, LIE 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.