State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Central Laboratory, The Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou 350001, China.
Exp Cell Res. 2018 Feb 1;363(1):73-83. doi: 10.1016/j.yexcr.2017.12.028. Epub 2017 Dec 30.
Dendritic cells (DCs) are pivotal to initiating adaptive immune response. Emerging evidence highlights important roles of tuberous sclerosis complex 1 (Tsc1) in DC development and activation. Our previous study also showed that Tsc1 expression in DCs was required to promote T-cell homeostasis and response partially through inhibiting mammalian target of rapamycin complex1 (mTORC1). However, the molecular mechanism of transcriptional regulation by which Tsc1 control DC homeostasis and function remains largely unknown. Here we globally identified the Tsc1-regulated genes by comparing the transcriptional profiling of Tsc1-deficient DCs with wild-type DCs. It showed that Tsc1 specifically regulated the expression of groups of gene sets critically involved in DC survival, proliferation, metabolism and antigen presentation. The impacts of Tsc1 on DC gene expression were partially dependent on inhibition of mTORC1 signal. Our study thus provides a comprehensive molecular basis for understanding how Tsc1 programs the homeostasis and function of DCs through transcriptional regulation.
树突状细胞（DCs）在启动适应性免疫反应中起着关键作用。新出现的证据强调了结节性硬化复合物 1（Tsc1）在 DC 发育和激活中的重要作用。我们之前的研究还表明，DC 中 Tsc1 的表达对于促进 T 细胞稳态和反应是必需的，部分是通过抑制雷帕霉素靶蛋白复合物 1（mTORC1）。然而，Tsc1 通过转录调控控制 DC 稳态和功能的分子机制在很大程度上仍是未知的。在这里，我们通过比较 Tsc1 缺陷型 DC 和野生型 DC 的转录谱，全局鉴定了 Tsc1 调控的基因。结果表明，Tsc1 特异性调节与 DC 存活、增殖、代谢和抗原呈递密切相关的基因集的表达。Tsc1 对 DC 基因表达的影响部分依赖于 mTORC1 信号的抑制。因此，我们的研究为理解 Tsc1 通过转录调控编程 DC 稳态和功能提供了一个全面的分子基础。
