Whole genome mRNA analysis of wild-type and Id2-deficient virus-specific CD8+ T cells after influenza infection. Mus musculus

The transcription factor Inhibitor of DNA binding 2 (Id2) modulates T cell fate decisions but the molecular mechanism underpinning this regulation is unclear. Here, using whole genome mRNA analysis we show that loss of Id2 programs CD8+ T cells to adopt a memory fate with increased Eomesodermin and Tcf7 expression. Our findings reveal that the Id2-E2A axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation. Overall design: Wild-type and Id2fl/flLckCre+ DbNP366-specific CD8+ T cells were isolated from the spleen of PR8-primed/HKx31-infected Ly5.2+Id2fl/flLckCre+:Ly5.1+ mixed bone marrow chimeric mice ten days after intranasal influenza infection and analysed by whole genome mRNA analysis. Three biological replicates of each genotype were subjected to microarray analysis.

转录因子DNA结合抑制因子2（Inhibitor of DNA binding 2，Id2）可调控T细胞命运决定，但支撑该调控过程的分子机制尚不明确。本研究通过全基因组mRNA分析发现，Id2缺失可使CD8+ T细胞定向获得记忆细胞命运，并伴随Eomesodermin与Tcf7表达水平上调。本研究结果揭示，Id2-E2A信号轴通过调控效应性与记忆性T细胞分化所必需的下游转录因子的诱导或抑制，从而调控T细胞分化进程。整体实验设计：将经PR8免疫后感染HKx31的Ly5.2+Id2fl/flLckCre+与Ly5.1+混合骨髓嵌合小鼠，在鼻内感染流感病毒10天后，分离其脾脏中野生型与Id2fl/flLckCre+两种基因型的DbNP366特异性CD8+ T细胞，采用全基因组mRNA分析进行检测；每个基因型设置3个生物学重复，进行基因芯片（microarray）分析。