Loss of CD4+ T Cell IL-6R Expression during Inflammation Underlines a Role for IL-6 Trans Signaling in the Local Maintenance of Th17 Cells
Loss of CD4+ T Cell IL-6R Expression during Inflammation Underlines a Role for IL-6 Trans Signaling in the Local Maintenance of Th17 Cells
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DOI：
10.4049/jimmunol.0901528
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发表时间：
2010-02-15
影响因子：
4.4
通讯作者：
Jones, Simon A.
中科院分区：
文献类型：
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作者：
Jones, Gareth W.;McLoughlin, Rachel M.;Jones, Simon A.
IL-6 反应通常通过膜结合的 IL-6R (CD126) α 亚基（经典 IL-6R 信号传导）或通过该同源受体的可溶形式（IL-6 反式信号传导）来协调。对人和小鼠 T 细胞上 IL-6R 表达的评估强调，IL-6R 表达与 CCR7 和 CD62L 密切相关。在这方面，来自临床和实验性腹膜炎发作的浸润效应T细胞失去TL-6R表达，并且体外外周T细胞的抗CD3/CD28 Ab共刺激导致IL-6R表达下调。因此，通过膜结合 IL-6R 的 IL-6 信号传导似乎仅限于幼稚或中央记忆 T 细胞群。活化的 T 细胞失去 IL-6R 表达进一步表明这些效应细胞可能仍通过 IL-6 反式信号传导保留 IL-6 反应性。使用IL-6R缺陷型小鼠和通过其可溶性受体调节IL-6信号传导能力的重组工具，我们报道了IL-6反式信号传导的局部控制调节T细胞浸润的效应器特征并促进分泌IL-17A的CD4+T细胞的维持。因此，我们得出结论，幼稚或中央记忆CD4+T细胞中的经典IL-6R信号传导需要引导其效应特性，而可溶性IL-6R活性的局部调节可能有助于维持Th细胞浸润的细胞因子谱。因此，T 细胞群的激活状态与 IL-6 反应性的改变有关。免疫学杂志，2010，184：2130-2139。
IL-6 responses are classically orchestrated via a membrane-bound IL-6R (CD126) alpha subunit (classical IL-6R signaling) or through a soluble form of this cognate receptor (IL-6 trans signaling). Appraisal of IL-6R expression on human and mouse T cells emphasized that IL-6R expression is closely linked with that of CCR7 and CD62L. In this regard, infiltrating effector T cells from clinical and experimental peritonitis episodes lose TL-6R expression, and anti-CD3/CD28 Ab costimulation of peripheral T cells in vitro leads to a downregulation in IL-6R expression. Consequently, IL-6 signaling through membrane-bound IL-6R seems to be limited to naive or central memory T cell populations. Loss of IL-6R expression by activated T cells further suggests that these effector cells might still retain IL-6 responsiveness via IL-6 trans signaling. Using IL-6R-deficient mice and recombinant tools that modulate the capacity of IL-6 to signal via its soluble receptor, we report that local control of IL-6 trans signaling regulates the effector characteristics of the T cell infiltrate and promotes the maintenance of IL-17A-secreting CD4(+) T cells. Therefore, we concluded that classical IL-6R signaling in naive or central memory CD4(+) T cells is required to steer their effector characteristics, whereas local regulation of soluble IL-6R activity might serve to maintain the cytokine profile of the Th cell infiltrate. Therefore, the activation status of a T cell population is linked with an alteration in IL-6 responsiveness. The Journal of Immunology, 2010,184: 2130-2139.