Department of Immunology, School of Basic Medical Sciences, Peking University, NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China.
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Cell Immunol. 2020 May;351:104065. doi: 10.1016/j.cellimm.2020.104065. Epub 2020 Feb 11.
Many aspects remain elusive of the mechanisms governing T cell quiescence. Here we show that E protein activity helps to establish a quiescent program in naïve T cells. Decreased E protein activity, as the consequence of enforced expression of an Id1 transgene, led to the accumulation of CD4CD44 T cells. The naïve CD4 T cells from this transgenic strain mounted a vigorous proliferative response upon TCR stimulation, as a result of direct inhibition of E protein activity. Transcriptome analyses demonstrated that Id1-tg naïve CD4 T cells exhibited a transcriptional profile characteristic of activated CD4 T cells, with particular enrichment in the gene set related to PI3K-AKT signaling. Western blot analysis confirmed low but constitutive activation of this pathway. Moreover, the Id1-tg CD4 T cells displayed enhanced formation of TCR microcluster. Taken together, these data support that downregulation of E protein activity facilitates the exit of naïve T cells from quiescence.
许多方面仍然难以捉摸的机制，调节 T 细胞静止。在这里，我们表明 E 蛋白的活性有助于建立一个静止的程序在幼稚 T 细胞。减少 E 蛋白的活性，作为必然的结果，强制表达的 Id1 转基因，导致积累的 CD4CD44 T 细胞。幼稚 CD4 T 细胞从这个转基因株系发起了一个积极的增殖反应后 TCR 刺激，由于直接抑制 E 蛋白的活性。转录组分析表明，Id1-tg 幼稚 CD4 T 细胞表现出一个转录特征的激活 CD4 T 细胞，特别是富集的基因集与 PI3K-AKT 信号通路。蛋白质印迹分析证实了低但组成性激活这条通路。此外，Id1-tg CD4 T 细胞显示增强的 TCR 微簇的形成。总的来说，这些数据支持下调 E 蛋白的活性有助于幼稚 T 细胞退出静止状态。
