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Histone lactylation drives CD8 + T cell metabolism and function.

Authors :
Raychaudhuri D
Singh P
Chakraborty B
Hennessey M
Tannir AJ
Byregowda S
Natarajan SM
Trujillo-Ocampo A
Im JS
Goswami S
Source :
Nature immunology [Nat Immunol] 2024 Nov; Vol. 25 (11), pp. 2140-2151. Date of Electronic Publication: 2024 Oct 07.
Publication Year :
2024

Abstract

The activation and functional differentiation of CD8 <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> T cells, which act as transcription initiators of key genes regulating CD8 <superscript>+</superscript> T cell function. Further, we note distinct patterns of H3K18la and H3K9la in CD8 <superscript>+</superscript> 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 <superscript>+</superscript> T cell effector function, including antitumor immunity, in preclinical models. Overall, our study uncovers the potential roles of H3K18la and H3K9la in CD8 <superscript>+</superscript> T cells.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Details

Language :
English
ISSN :
1529-2916
Volume :
25
Issue :
11
Database :
MEDLINE
Journal :
Nature immunology
Publication Type :
Academic Journal
Accession number :
39375549
Full Text :
https://doi.org/10.1038/s41590-024-01985-9