title: Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease.
abstract: 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-7Ralpha 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.
authors.affiliation: Department of Neuroimmunology, GlaxoSmithKline Research and Development Center, Shanghai, China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Liu
authors.forename: Stewart
authors.initials: S
authors.lastname: Leung
authors.forename: Chunxia
authors.initials: C
authors.lastname: Wang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Tan
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.forename: Taylor B
authors.initials: TB
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Wan
authors.forename: Xia
authors.initials: X
authors.lastname: Qin
authors.forename: Limin
authors.initials: L
authors.lastname: Lu
authors.forename: Runsheng
authors.initials: R
authors.lastname: Li
authors.forename: Heng
authors.initials: H
authors.lastname: Pan
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Song
authors.forename: Ailian
authors.initials: A
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.forename: Hongtao
authors.initials: H
authors.lastname: Lu
authors.forename: Jingwu Z
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology*; D053612:Janus Kinases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D050799:STAT5 Transcription Factor / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*
chemical_list: D015851:Interleukin-7; D050799:STAT5 Transcription Factor; D053612:Janus Kinases