PDF(Pubmed)
Abstract：
This research investigates the intricate dynamics of DNA methylation in the hours following CD8+ T cell activation, during a critical yet understudied temporal window. DNA methylation is an epigenetic modification central to regulation of gene expression and directing immune responses. Our investigation spanned 96-h post-activation and unveils a nuanced tapestry of global and site-specific methylation changes. We identified 15,626 significant differentially methylated CpGs spread across the genome, with the most significant changes occurring within the genes ADAM10, ICA1, and LAPTM5. While many changes had modest effect sizes, approximately 120 CpGs exhibited a log2FC above 1.5, with cell activation and proliferation pathways the most affected. Relatively few of the differentially methylated CpGs occurred along adjacent gene regions. The exceptions were seven differentially methylated gene regions, with the Human T cell Receptor Alpha Joining Genes demonstrating consistent methylation change over a 3kb window. We also investigated whether an inflammatory environment could alter DNA methylation during activation, with proliferating cells exposed to the oxidant glycine chloramine. No substantial differential methylation was observed in this context. The temporal perspective of early activation adds depth to the evolving field of epigenetic immunology, offering insights with implications for therapeutic innovation and expanding our understanding of epigenetic modulation in immune function.
摘要：
这项研究调查了CD8+T细胞活化后数小时内DNA甲基化的复杂动态，在一个关键但研究不足的时间窗口。DNA甲基化是调节基因表达和指导免疫反应的核心表观遗传修饰。我们的调查跨越了激活后96小时，并揭示了全球和位点特异性甲基化变化的细微差别。我们确定了15,626个显着的差异甲基化CpG分布在整个基因组中，最显著的变化发生在基因ADAM10、ICA1和LAPTM5内。虽然许多变化具有适度的效应大小，大约120个CpG表现出高于1.5的log2FC,其中细胞活化和增殖途径受影响最大。相对较少的差异甲基化CpG沿着相邻的基因区域发生。例外是七个差异甲基化基因区域，人类T细胞受体α连接基因在3kb窗口内表现出一致的甲基化变化。我们还研究了炎症环境是否可以在激活过程中改变DNA甲基化，增殖细胞暴露于氧化剂甘氨酸氯胺。在这种情况下没有观察到实质性的差异甲基化。早期激活的时间视角为表观遗传免疫学的发展领域增加了深度，提供具有治疗创新意义的见解，并扩大我们对免疫功能中表观遗传调节的理解。
