Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
J Immunol. 2011 Jan 15;186(2):969-76. doi: 10.4049/jimmunol.1002099. Epub 2010 Dec 10.
The expression of CD127, the IL-7-binding subunit of the IL-7 R, is tightly regulated during the development and activation of T cells and is reduced during chronic viral infection. However, the molecular mechanism regulating the dynamic expression of CD127 is still poorly understood. In this study, we report that the transcription factor Ets-1 is required for maintaining the expression of CD127 in murine peripheral T cells. Ets-1 binds to and activates the CD127 promoter, and its absence leads to reduced CD127 expression, attenuated IL-7 signaling, and impaired IL-7-dependent homeostatic proliferation of T cells. The expression of CD127 and Ets-1 is strongly correlated in human T cells. Both CD127 and Ets-1 expression are decreased in CD8(+) T cells during HIV infection. In addition, HIV-associated loss of CD127 is only observed in Ets-1(low) effector memory and central memory but not in Ets-1(high) naive CD8(+) T cells. Taken together, our data identify Ets-1 as a critical regulator of CD127 expression in T cells.
CD127 的表达，即白细胞介素 7 受体（IL-7R）的 IL-7 结合亚基，在 T 细胞的发育和激活过程中受到严格调控，并在慢性病毒感染期间降低。然而，调节 CD127 动态表达的分子机制仍知之甚少。在这项研究中，我们报告转录因子 Ets-1 是维持小鼠外周 T 细胞 CD127 表达所必需的。Ets-1 结合并激活 CD127 启动子，其缺失导致 CD127 表达减少、IL-7 信号减弱以及 IL-7 依赖性 T 细胞稳态增殖受损。在人类 T 细胞中，CD127 和 Ets-1 的表达强烈相关。在 HIV 感染期间，CD8(+) T 细胞中 CD127 和 Ets-1 的表达均降低。此外，仅在 Ets-1(low)效应记忆和中央记忆 CD8(+) T 细胞中观察到 HIV 相关的 CD127 丢失，而在 Ets-1(high)幼稚 CD8(+) T 细胞中则没有。总之，我们的数据将 Ets-1 确定为 T 细胞中 CD127 表达的关键调节剂。
