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.