Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease.
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.
Liu
Xuebin
X
Department of Neuroimmunology, GlaxoSmithKline Research and Development Center, Shanghai, China.
Leung
Stewart
S
Wang
Chunxia
C
Tan
Zhu
Z
Wang
Ji
J
Guo
Taylor B
TB
Fang
Lei
L
Zhao
Yonggang
Y
Wan
Bing
B
Qin
Xia
X
Lu
Limin
L
Li
Runsheng
R
Pan
Heng
H
Song
Mingjuan
M
Liu
Ailian
A
Hong
Jian
J
Lu
Hongtao
H
Zhang
Jingwu Z
JZ
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*
D015851:Interleukin-7; D050799:STAT5 Transcription Factor; D053612:Janus Kinases