Nutrient-driven histone code determines exhausted CD8+ T cell fates
Ma S, Dahabieh M, Mann T, Zhao S, McDonald B, Song W, Chung H, Farsakoglu Y, Garcia-Rivera L, Hoffmann F, Xu S, Du V, Chen D, Furgiuele J, LaPorta M, Jacobs E, DeCamp L, Oswald B, Sheldon R, Ellis A, Liu L, He P, Wang Y, Jang C, Jones R, Kaech S. Nutrient-driven histone code determines exhausted CD8+ T cell fates. Science 2024, eadj3020. PMID: 39666821, DOI: 10.1126/science.adj3020.Peer-Reviewed Original ResearchATP-citrate lyaseAcetyl-CoA synthetase 2Histone codeCD8<sup>+</sup> T cell differentiationTumor-specific T-cell responsesACLY inhibitionHistone acetylationCD8+ T cell fateExhausted T cellsT-cell therapyChronic viral infectionsT cell responsesT cell differentiationT cell fateT cell genesTex cellsT cellsEpigenetic modificationsEpigenetic remodelingViral infectionCitrate metabolismNutrient metabolismHistoneAcetylationDifferentiationACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses
Kaymak I, Watson M, Oswald B, Ma S, Johnson B, DeCamp L, Mabvakure B, Luda K, H. E, Lau K, Fu Z, Muhire B, Kitchen-Goosen S, Vander Ark A, Dahabieh M, Samborska B, Vos M, Shen H, Fan Z, Roddy T, Kingsbury G, Sousa C, Krawczyk C, Williams K, Sheldon R, Kaech S, Roy D, Jones R. ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses. Journal Of Experimental Medicine 2024, 221: e20231820. PMID: 39150482, PMCID: PMC11329787, DOI: 10.1084/jem.20231820.Peer-Reviewed Original ResearchConceptsAcyl-CoA synthetase short-chain family member 2Acetyl-CoA productionATP citrate lyaseChromatin accessibilityAcetyl-CoAEnzyme ATP citrate lyaseFamily member 2Function in vivoCoordination of cellular metabolismTCA cycleMetabolic nodesGene locusCitrate lyaseT cell effector responsesHistone acetylationCellular metabolismEffector functionsCD8 T cellsResponse to infectionMember 2ChromatinEffector responsesMetabolic substratesT cell response to infectionT cells