Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease (Retracted article. See vol. 19, pg. 1673, 2013)
Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease (Retracted article. See vol. 19, pg. 1673, 2013)
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DOI：
10.1038/nm.2077
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发表时间：
2010-02-01
期刊：
影响因子：
82.9
通讯作者：
Zhang, Jingwu Z.
中科院分区：
文献类型：
--
作者：
Liu, Xuebin;Leung, Stewart;Zhang, Jingwu Z.
白细胞介素 7 受体 (IL-7R) 在遗传上与多发性硬化症的易感性相关。在这里，我们描述了 IL-7 对于实验性自身免疫性脑脊髓炎 (EAE) 中致病性 T 辅助型 17 (T(H)17) 细胞的生存和扩张至关重要。 IL-7 直接扩增 EAE 中的效应 T(H)17 细胞和来自多发性硬化症受试者的人 T(H)17 细胞，而 T(H)17 分化不需要它。 IL-7R 拮抗作用通过抑制 Janus 激酶信号转导器和转录激活剂 5 (JAK-STAT5) 通路并改变促存活蛋白 Bcl-2 和促凋亡蛋白 Bax 的表达，使分化的 T(H)17 细胞易于凋亡，从而降低 EAE 的严重程度。相比之下，T(H)1 和调节性 T (T-reg) 细胞在体内对 IL-7R 拮抗作用不太敏感或不受其影响。这种选择性归因于 T-reg 细胞中 IL-7R α 的最低表达，并与 T(H)1 细胞中高水平的 Socs1（编码细胞因子信号传导抑制因子 1）表达相关。该研究揭示了 IL-7-IL-7R 在 T(H)17 细胞存活和扩增中的独特的、先前未描述的作用，并对自身免疫性疾病的治疗具有重要意义。
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-7R alpha 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.