FOXP3 protects conventional human T cells from premature restimulation-induced cell death

Transcriptome profiling and functional analyses on expanding Tcons revealed that FOXP3 enhances expression of the SLAM family receptor CD48, which in turn sustains basal autophagy and suppresses pro-apoptotic p53 signaling. Our findings suggest that FOXP3 governs a distinct transcriptional program in early-stage effector Tcons that maintains RICD resistance via CD48-dependent protective autophagy and p53 suppression. Purified human CD4 T cells were electroporated with siRNAs against FOXP3 or negative-control medum GC duplex siRNA and differential gene expression analysis was performed using mRNA sequencing.针对扩增中的常规T细胞（Tcons）开展的转录组谱分析与功能实验显示，叉头框蛋白P3（FOXP3）可上调信号淋巴细胞激活分子家族受体CD48的表达，而CD48继而可维持基础自噬水平并抑制促凋亡p53信号通路。本研究结果表明，FOXP3可在早期效应性常规T细胞中调控一套独特的转录程序，该程序通过CD48依赖性的保护性自噬及p53抑制作用，维持细胞对再刺激诱导细胞死亡（RICD）的抗性。将纯化的人CD4阳性T细胞分别电转染靶向FOXP3的小干扰RNA（siRNA）以及阴性对照中等GC含量双链siRNA，随后通过mRNA测序完成差异基因表达分析。