美国德克萨斯大学Sangeeta Goswami研究小组发现，组蛋白乳酸化驱动CD8⁺ T细胞的代谢和功能。该项研究成果于2024年10月7日在线发表在《自然—免疫学》杂志上。

研究人员发现，人类和小鼠CD8⁺ T细胞中H3K18乳酸化（H3K18la）和H3K9乳酸化（H3K9la）的富集，这些修饰作为调节CD8⁺ T细胞功能的关键基因的转录起始子。此外，研究人员注意到CD8⁺ T细胞亚群中H3K18la和H3K9la的不同模式，这与它们特定的代谢谱相关。

此外，研究人员发现通过靶向代谢和表观遗传途径调节H3K18la和H3K9la会影响CD8⁺ T细胞的效应功能，包括在临床前模型中的抗肿瘤免疫。

总体而言，该研究揭示了H3K18la和H3K9la在CD8⁺ T细胞中的潜在作用。

据介绍，CD8⁺ T细胞的激活和功能分化与代谢途径相关，这些途径导致乳酸的产生。乳酸化是一种源自乳酸的组蛋白翻译后修饰；然而，组蛋白乳酸化在CD8+ T细胞激活和功能中的相关性尚不清楚。

附：英文原文

Title: Histone lactylation drives CD8+ T cell metabolism and function

Author: Raychaudhuri, Deblina, Singh, Pratishtha, Chakraborty, Bidisha, Hennessey, Mercedes, Tannir, Aminah J., Byregowda, Shrinidhi, Natarajan, Seanu Meena, Trujillo-Ocampo, Abel, Im, Jin Seon, Goswami, Sangeeta

Issue&Volume: 2024-10-07

Abstract: 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.

DOI: 10.1038/s41590-024-01985-9

Source: https://www.nature.com/articles/s41590-024-01985-9