Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Department of Anatomy, Pusan National University School of Medicine, Yangsan 626-870, South-Korea.
Sci Rep. 2016 Nov 11;6:36962. doi: 10.1038/srep36962.
The soluble γc protein (sγc) is a naturally occurring splice isoform of the γc cytokine receptor that is produced by activated T cells and inhibits γc cytokine signaling. Here we show that sγc expression is also highly upregulated in immature CD4CD8 thymocytes but then downregulated in mature thymocytes. These results indicate a developmentally controlled mechanism for sγc expression and suggest a potential role for sγc in regulating T cell development in the thymus. Indeed, sγc overexpression resulted in significantly reduced thymocyte numbers and diminished expansion of immature thymocytes, concordant to its role in suppressing signaling by IL-7, a critical γc cytokine in early thymopoiesis. Notably, sγc overexpression also impaired generation of iNKT cells, resulting in reduced iNKT cell percentages and numbers in the thymus. iNKT cell development requires IL-15, and we found that sγc interfered with IL-15 signaling to suppress iNKT cell generation in the thymus. Thus, sγc represents a new mechanism to control cytokine availability during T cell development that constrains mature T cell production and specifically iNKT cell generation in the thymus.
可溶性 γc 蛋白 (sγc) 是 γc 细胞因子受体的一种天然剪接异构体，由活化的 T 细胞产生，可抑制 γc 细胞因子信号转导。本文作者表明，sγc 的表达在未成熟的 CD4CD8 胸腺细胞中也高度上调，但在成熟的胸腺细胞中下调。这些结果表明 sγc 表达存在一种发育调控机制，并提示 sγc 在调节胸腺中 T 细胞发育方面可能具有重要作用。事实上，sγc 的过表达导致胸腺细胞数量显著减少，未成熟胸腺细胞的扩增减少，这与其在抑制 IL-7 信号转导中的作用一致，IL-7 是早期胸腺生成中的一种关键 γc 细胞因子。值得注意的是，sγc 的过表达也损害了 iNKT 细胞的生成，导致胸腺中 iNKT 细胞的比例和数量减少。iNKT 细胞的发育需要 IL-15，作者发现 sγc 干扰了 IL-15 信号转导，从而抑制了胸腺中 iNKT 细胞的生成。因此，sγc 代表了一种新的机制，可以在 T 细胞发育过程中控制细胞因子的可用性，从而限制成熟 T 细胞的产生和特定的 iNKT 细胞在胸腺中的生成。
