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

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.