Lysine methyltransferase Kmt2d regulates naive CD8+ T cell activation-induced survival

作者：Jae‐Kwan Kim, Thomas Nguyen, Jeffrey Cifello, Raheel Ahmad, Yongqing Zhang, Qian Yang, Ji‐Eun Lee, Xiang Li, Kai Yan, Supriyo De, Weiqun Peng, Kai Ge, Nan‐ping Weng · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2022.1095140 · 被引用次数：8 · 研究领域：Epigenetics and DNA Methylation、Immune Cell Function and Interaction、Cancer-related gene regulation

Lysine specific methyltransferase 2D (Kmt2d) catalyzes the mono-methylation of histone 3 lysine 4 (H3K4me1) and plays a critical role in regulatory T cell generation via modulating Foxp3 gene expression. Here we report a role of Kmt2d in naïve CD8 + T cell generation and survival. In the absence of Kmt2d , the number of CD8 + T cells, particularly naïve CD8 + T cells (CD62L hi /CD44 lo ), in spleen was greatly decreased and in vitro activation-related death significantly increased from Kmt2d fl/fl CD4cre + (KO) compared to Kmt2d fl/fl CD4cre - (WT) mice. Furthermore, analyses by ChIPseq, RNAseq, and scRNAseq showed reduced H3K4me1 levels in enhancers and reduced expression of apoptosis-related genes in activated naïve CD8 + T cells in the absence of Kmt2d. Finally, we confirmed the activation-induced death of antigen-specific naïve CD8 + T cells in vivo in Kmt2d KO mice upon challenge with Listeria monocytogenes infection. These findings reveal that Kmt2d regulates activation-induced naïve CD8 + T cell survival via modulating H3K4me1 levels in enhancer regions of apoptosis and immune function-related genes.