title: Leukemia inhibitory factor inhibits T helper 17 cell differentiation and confers treatment effects of neural progenitor cell therapy in autoimmune disease.
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.
authors.affiliation: Institute of Health Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences and Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhengyi
authors.initials: Z
authors.lastname: Wang
authors.forename: Ailian
authors.initials: A
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.forename: Fenglan
authors.initials: F
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.forename: Stewart
authors.initials: S
authors.lastname: Leung
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.forename: Jingwu Z
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy; D009474:Neurons / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases