Leukemia Inhibitory Factor Inhibits T Helper 17 Cell Differentiation and Confers Treatment Effects of Neural Progenitor Cell Therapy in Autoimmune Disease
Autor: | Wei Cao, Zhengyi Wang, Yiqing Yang, Ailian Liu, Chen Dong, Yufang Shi, Jingwu Z Zhang, Fenglan Wu, Stewart Leung, Jian Hong, Lei Fang |
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Rok vydání: | 2011 |
Předmět: |
STAT3 Transcription Factor
Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Cellular differentiation Receptor expression Immunology Suppressor of Cytokine Signaling Proteins Biology Leukemia Inhibitory Factor Article Interferon-gamma Mice otorhinolaryngologic diseases medicine Animals Humans Immunology and Allergy T helper 17 cell SOCS3 Progenitor cell Extracellular Signal-Regulated MAP Kinases STAT3 Cells Cultured Mice Knockout Neurons Interleukin-6 Stem Cells Experimental autoimmune encephalomyelitis Cell Differentiation medicine.disease Mice Inbred C57BL stomatognathic diseases Disease Models Animal Infectious Diseases Suppressor of Cytokine Signaling 3 Protein Cancer research biology.protein Th17 Cells Leukemia inhibitory factor Stem Cell Transplantation |
Zdroj: | Immunity. 35:273-284 |
ISSN: | 1074-7613 |
Popis: | SummaryNeural 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. |
Databáze: | OpenAIRE |
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