CD8 T 细胞的激活和功能分化与导致乳酸产生的代谢途径有关。乳酰化是一种乳酸衍生的组蛋白翻译后修饰；然而，组蛋白乳酰化与 CD8 T 细胞激活和功能的相关性尚不清楚。在这里，我们展示了人和小鼠 CD8 T 细胞中 H3K18 乳酰化 (H3K18la) 和 H3K9 乳酰化 (H3K9la) 的富集，它们充当调节 CD8 T 细胞功能的关键基因的转录起始子。此外，我们注意到 CD8 T 细胞亚群中 H3K18la 和 H3K9la 的不同模式与其特定的代谢谱相关。此外，我们发现在临床前模型中，通过靶向代谢和表观遗传途径来调节 H3K18la 和 H3K9la 会影响 CD8 T 细胞效应功能，包括抗肿瘤免疫。总体而言，我们的研究揭示了 H3K18la 和 H3K9la 在 CD8 T 细胞中的潜在作用。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

The activation and functional differentiation of CD8+ T cells are linked to metabolic pathways that result in the production of lactate. Lactylation is a lactate-derived histone post-translational modification; however, the relevance of histone lactylation in the context of CD8+ T cell activation and function is not known. Here, we show the enrichment of H3K18 lactylation (H3K18la) and H3K9 lactylation (H3K9la) in human and mouse CD8+ T cells, which act as transcription initiators of key genes regulating CD8+ T cell function. Further, we note distinct patterns of H3K18la and H3K9la in CD8+ T cell subsets linked to their specific metabolic profiles. Additionally, we find that modulation of H3K18la and H3K9la by targeting metabolic and epigenetic pathways influence CD8+ T cell effector function, including antitumor immunity, in preclinical models. Overall, our study uncovers the potential roles of H3K18la and H3K9la in CD8+ T cells.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.