Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease

• Published in: Nature medicine Vol. 16; no. 2; pp. 191 - 197
• Main Authors: Liu, Xuebin, Leung, Stewart, Wang, Chunxia, Tan, Zhu, Wang, Ji, Guo, Taylor B, Fang, Lei, Zhao, Yonggang, Wan, Bing, Qin, Xia, Lu, Limin, Li, Runsheng, Pan, Heng, Song, Mingjuan, Liu, Ailian, Hong, Jian, Lu, Hongtao, Zhang, Jingwu Z
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2010; Nature Publishing Group
• Subjects: 631/250/127/1213; 631/250/1619/554/1898/1273; 631/80/86; 692/699/249/1313/1666; Animals; Apoptosis; Autoimmune diseases; BAX protein; Bcl-2 protein; Biomedical and Life Sciences; Biomedical research; Biomedicine; Cancer Research; Care and treatment; Cell Differentiation; Cell survival; Cytokines; Development and progression; Effector cells; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - immunology; Experimental allergic encephalomyelitis; Gene expression; Health aspects; Helper cells; Infectious Diseases; Interleukin 7; Interleukin-7 - immunology; Interleukins; Janus kinase; Janus Kinases - metabolism; Kinases; Lymphocytes; Lymphocytes T; Medical schools; Metabolic Diseases; Mice; Mice, Transgenic; Molecular Medicine; Multiple sclerosis; Neurosciences; Prevention; Proteins; Selectivity; Signal transduction; SOCS-1 protein; Stat5 protein; STAT5 Transcription Factor - metabolism; Survival; T-Lymphocytes, Helper-Inducer - cytology; Transcription; United States; China
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/nm.2077

Variation in the IL-7 receptor is associated with susceptibility to multiple sclerosis. Jingwu Zhang and his colleagues provide an explanation. They show that the cytokine IL-7 regulates the surival and proliferation of T helper type 17 cells—a cell type known to be involved in the pathogenesis of multiple sclerosis. The findings suggest that IL-7 antagonism could be useful in individuals with autoimmune diseases such as multiple sclerosis ( pages 166–168 ). Interleukin-7 receptor (IL-7R) is genetically associated with susceptibility to multiple sclerosis. Here we describe that IL-7 is essential for survival and expansion of pathogenic T helper type 17 (T H 17) cells in experimental autoimmune encephalomyelitis (EAE). IL-7 directly expanded effector T H 17 cells in EAE and human T H 17 cells from subjects with multiple sclerosis, whereas it was not required for T H 17 differentiation. IL-7R antagonism rendered differentiated T H 17 cells susceptible to apoptosis through the inhibition of Janus kinase–signal transducer and activator of transcription-5 (JAK-STAT5) pathway and altered expression of the prosurvival protein Bcl-2 and the proapoptotic protein Bax, leading to decreased severity of EAE. In contrast, T H 1 and regulatory T (T reg ) cells were less susceptible to or not affected by IL-7R antagonism in vivo . The selectivity was attributable to minimal expression of IL-7Rα in T reg cells and correlated with a high level of Socs1 (encoding suppressor of cytokine signaling-1) expression in T H 1 cells. The study reveals a unique, previously undescribed role of IL-7–IL-7R in T H 17 cell survival and expansion and has implications in the treatment of autoimmune disease.