CD8型
细胞毒性T细胞
细胞生物学
T细胞
生物
效应器
组蛋白
表观遗传学
表型
功能(生物学)
免疫系统
基因
遗传学
体外
作者
Deblina Raychaudhuri,Pratishtha Singh,Mercedes Hennessey,Bidisha Chakraborty,Aminah J. Tannir,Abel Trujillo‐Ocampo,Jin S. Im,Sangeeta Goswami
标识
DOI:10.1101/2023.08.25.554830
摘要
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 (hPTM); 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 murine CD8 T cells which act as transcription initiators of key genes regulating CD8 T cell phenotype and function. Further, we note distinct impacts of H3K18la and H3K9la on CD8 T cell subsets linked to their specific metabolic profiles. Importantly, we demonstrate that modulation of H3K18la and H3K9la by targeting metabolic and epigenetic pathways regulates CD8 T cell effector function including anti-tumor immunity in preclinical models. Overall, our study uncovers the unique contributions of H3K18la and H3K9la in modulating CD8 T cell phenotype and function intricately associated with metabolic state.
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