Interleukin-7 promotes the survival of human CD4+effector/memory T cells by up-regulating Bcl-2 proteins and activating the JAK/STAT signalling pathway
Interleukin-7 promotes the survival of human CD4+effector/memory T cells by up-regulating Bcl-2 proteins and activating the JAK/STAT signalling pathway
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DOI：
10.1111/j.1365-2567.2009.03244.x
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发表时间：
2010-07-01
期刊：
影响因子：
6.4
通讯作者：
Aoudjit, Fawzi
中科院分区：
文献类型：
--
作者：
Chetoui, Nizar;Boisvert, Marc;Aoudjit, Fawzi
白细胞介素 7 (IL-7) 是一种参与 T 细胞存活和发育的重要细胞因子，但其在人类 T 细胞（特别是效应/记忆 T 细胞）中的信号传导却鲜有记录。在这项研究中，我们发现 IL-7 可以保护人 CD4+ 效应/记忆 T 细胞免于在缺乏刺激和细胞因子的情况下诱导细胞凋亡。我们发现 IL-7 不仅上调 Bcl-2，还上调 Bcl-xL 和 Mcl-1。 Interleukin-7 诱导的 janus 激酶/信号转导器和转录激活剂 (JAK/STAT) 信号通路的激活足以维持细胞存活和 Bcl-2 蛋白的上调。与之前对初始 T 细胞的研究相比，我们发现 IL-7 是磷脂酰肌醇 3 激酶 (PI3K)/AKT（也称为蛋白激酶 B）通路的弱激活剂，IL-7 介导的细胞存活独立于 PI3K/AKT 通路以及丝裂原激活蛋白激酶/细胞外信号调节激酶通路的激活而发生。考虑到 IL-7 和 CD4+ 效应/记忆 T 细胞对类风湿性关节炎和结肠炎等自身免疫性疾病发病机制的贡献，我们的研究表明 IL-7 可以通过促进细胞存活来促进这些疾病。进一步了解与自身免疫炎症性疾病相关的效应/记忆 T 细胞中 IL-7 信号转导机制可能会带来潜在的新治疗途径。
P>Interleukin-7 (IL-7) is a crucial cytokine involved in T-cell survival and development but its signalling in human T cells, particularly in effector/memory T cells, is poorly documented. In this study, we found that IL-7 protects human CD4+ effector/memory T cells from apoptosis induced upon the absence of stimulation and cytokines. We show that IL-7 up-regulates not only Bcl-2 but also Bcl-xL and Mcl-1 as well. Interleukin-7-induced activation of the janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is sufficient for cell survival and up-regulation of Bcl-2 proteins. In contrast to previous studies with naive T cells, we found that IL-7 is a weak activator of the phosphatidylinositol 3 kinase (PI3K)/AKT (also referred as protein kinase B) pathway and IL-7-mediated cell survival occurs independently from the PI3K/AKT pathway as well as from activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Considering the contribution of both IL-7 and CD4+ effector/memory T cells to the pathogenesis of autoimmune diseases such as rheumatoid arthritis and colitis, our study suggests that IL-7 can contribute to these diseases by promoting cell survival. A further understanding of the mechanisms of IL-7 signalling in effector/memory T cells associated with autoimmune inflammatory diseases may lead to potential new therapeutic avenues.