Histone lactylation drives CD8 + T cell metabolism and function.

Autor: Raychaudhuri D; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Singh P; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Chakraborty B; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hennessey M; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Tannir AJ; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Byregowda S; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Natarajan SM; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Trujillo-Ocampo A; Department of Hematopoietic Biology and Malignancy, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA., Im JS; Department of Hematopoietic Biology and Malignancy, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA.; The University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.; Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA., Goswami S; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. sgoswami@mdanderson.org.; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. sgoswami@mdanderson.org.; James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. sgoswami@mdanderson.org.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Nov; Vol. 25 (11), pp. 2140-2151. Date of Electronic Publication: 2024 Oct 07.
DOI: 10.1038/s41590-024-01985-9
Abstrakt: 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.)
Databáze: MEDLINE
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