Leukemia Inhibitory Factor Inhibits T Helper 17 Cell Differentiation and Confers Treatment Effects of Neural Progenitor Cell Therapy in Autoimmune Disease

Wei Cao, Yiqing Yang, Zhengyi Wang, Ailian Liu, Lei Fang, Fenglan Wu, Jian Hong, Yufang Shi, Stewart Leung, Chen Dong, Jingwu Z. Zhang

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)273-284
Number of pages12
JournalImmunity
Volume35
Issue number2
DOIs
StatePublished - Aug 26 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology

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