Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Immunity. 2014 Jun 19;40(6):910-23. doi: 10.1016/j.immuni.2014.04.020. Epub 2014 Jun 5.
The common γ-chain (γc) plays a central role in signaling by IL-2 and other γc-dependent cytokines. Here we report that activated T cells produce an alternatively spliced form of γc mRNA that results in protein expression and secretion of the γc extracellular domain. The soluble form of γc (sγc) is present in serum and directly binds to IL-2Rβ and IL-7Rα proteins on T cells to inhibit cytokine signaling and promote inflammation. sγc suppressed IL-7 signaling to impair naive T cell survival during homeostasis and exacerbated Th17-cell-mediated inflammation by inhibiting IL-2 signaling upon T cell activation. Reciprocally, the severity of Th17-cell-mediated inflammatory diseases was markedly diminished in mice lacking sγc. Thus, sγc expression is a naturally occurring immunomodulator that regulates γc cytokine signaling and controls T cell activation and differentiation.
共同γ链（γc）在 IL-2 和其他 γc 依赖性细胞因子的信号转导中发挥核心作用。在这里，我们报告说，活化的 T 细胞产生 γc mRNA 的一种选择性剪接形式，导致 γc 细胞外结构域的蛋白表达和分泌。γc 的可溶性形式（sγc）存在于血清中，并直接与 T 细胞上的 IL-2Rβ 和 IL-7Rα 蛋白结合，抑制细胞因子信号转导并促进炎症。sγc 抑制 IL-7 信号转导，在体内平衡期间损害幼稚 T 细胞的存活，并通过在 T 细胞活化时抑制 IL-2 信号转导，加重 Th17 细胞介导的炎症。相反，缺乏 sγc 的小鼠中 Th17 细胞介导的炎症性疾病的严重程度明显降低。因此，sγc 的表达是一种天然存在的免疫调节剂，可调节 γc 细胞因子信号转导，并控制 T 细胞的激活和分化。
