Ketolysis drives CD8+ T cell effector function through effects on histone acetylation

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Ketolysis drives CD8+ T cell effector function through effects on histone acetylation. / Luda, Katarzyna M.; Longo, Joseph; Kitchen-Goosen, Susan M.; Duimstra, Lauren R.; Ma, Eric H.; Watson, McLane J.; Oswald, Brandon M.; Fu, Zhen; Madaj, Zachary; Kupai, Ariana; Dickson, Bradley M.; DeCamp, Lisa M.; Dahabieh, Michael S.; Compton, Shelby E.; Teis, Robert; Kaymak, Irem; Lau, Kin H.; Kelly, Daniel P.; Puchalska, Patrycja; Williams, Kelsey S.; Krawczyk, Connie M.; Lévesque, Dominique; Boisvert, François Michel; Sheldon, Ryan D.; Rothbart, Scott B.; Crawford, Peter A.; Jones, Russell G.

In: Immunity, Vol. 56, No. 9, 2023, p. 2021-2035.e8.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Luda, KM, Longo, J, Kitchen-Goosen, SM, Duimstra, LR, Ma, EH, Watson, MJ, Oswald, BM, Fu, Z, Madaj, Z, Kupai, A, Dickson, BM, DeCamp, LM, Dahabieh, MS, Compton, SE, Teis, R, Kaymak, I, Lau, KH, Kelly, DP, Puchalska, P, Williams, KS, Krawczyk, CM, Lévesque, D, Boisvert, FM, Sheldon, RD, Rothbart, SB, Crawford, PA & Jones, RG 2023, 'Ketolysis drives CD8+ T cell effector function through effects on histone acetylation', Immunity, vol. 56, no. 9, pp. 2021-2035.e8. https://doi.org/10.1016/j.immuni.2023.07.002

APA

Luda, K. M., Longo, J., Kitchen-Goosen, S. M., Duimstra, L. R., Ma, E. H., Watson, M. J., Oswald, B. M., Fu, Z., Madaj, Z., Kupai, A., Dickson, B. M., DeCamp, L. M., Dahabieh, M. S., Compton, S. E., Teis, R., Kaymak, I., Lau, K. H., Kelly, D. P., Puchalska, P., ... Jones, R. G. (2023). Ketolysis drives CD8+ T cell effector function through effects on histone acetylation. Immunity, 56(9), 2021-2035.e8. https://doi.org/10.1016/j.immuni.2023.07.002

Vancouver

Luda KM, Longo J, Kitchen-Goosen SM, Duimstra LR, Ma EH, Watson MJ et al. Ketolysis drives CD8+ T cell effector function through effects on histone acetylation. Immunity. 2023;56(9):2021-2035.e8. https://doi.org/10.1016/j.immuni.2023.07.002

Author

Luda, Katarzyna M. ; Longo, Joseph ; Kitchen-Goosen, Susan M. ; Duimstra, Lauren R. ; Ma, Eric H. ; Watson, McLane J. ; Oswald, Brandon M. ; Fu, Zhen ; Madaj, Zachary ; Kupai, Ariana ; Dickson, Bradley M. ; DeCamp, Lisa M. ; Dahabieh, Michael S. ; Compton, Shelby E. ; Teis, Robert ; Kaymak, Irem ; Lau, Kin H. ; Kelly, Daniel P. ; Puchalska, Patrycja ; Williams, Kelsey S. ; Krawczyk, Connie M. ; Lévesque, Dominique ; Boisvert, François Michel ; Sheldon, Ryan D. ; Rothbart, Scott B. ; Crawford, Peter A. ; Jones, Russell G. / Ketolysis drives CD8+ T cell effector function through effects on histone acetylation. In: Immunity. 2023 ; Vol. 56, No. 9. pp. 2021-2035.e8.

Bibtex

@article{64379af8dd434656ac496ecf3d968be0,
title = "Ketolysis drives CD8+ T cell effector function through effects on histone acetylation",
abstract = "Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies (KBs)—including β-hydroxybutyrate (βOHB) and acetoacetate (AcAc)—as essential fuels supporting CD8+ T cell metabolism and effector function. βOHB directly increased CD8+ T effector (Teff) cell cytokine production and cytolytic activity, and KB oxidation (ketolysis) was required for Teff cell responses to bacterial infection and tumor challenge. CD8+ Teff cells preferentially used KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boosted the respiratory capacity and TCA cycle-dependent metabolic pathways that fuel CD8+ T cell function. Mechanistically, βOHB was a major substrate for acetyl-CoA production in CD8+ T cells and regulated effector responses through effects on histone acetylation. Together, our results identify cell-intrinsic ketolysis as a metabolic and epigenetic driver of optimal CD8+ T cell effector responses.",
keywords = "acetyl-CoA, cancer immunology, CD8 T cells, effector function, epigenetics, ketolysis, ketone bodies, metabolism, TCA cycle",
author = "Luda, {Katarzyna M.} and Joseph Longo and Kitchen-Goosen, {Susan M.} and Duimstra, {Lauren R.} and Ma, {Eric H.} and Watson, {McLane J.} and Oswald, {Brandon M.} and Zhen Fu and Zachary Madaj and Ariana Kupai and Dickson, {Bradley M.} and DeCamp, {Lisa M.} and Dahabieh, {Michael S.} and Compton, {Shelby E.} and Robert Teis and Irem Kaymak and Lau, {Kin H.} and Kelly, {Daniel P.} and Patrycja Puchalska and Williams, {Kelsey S.} and Krawczyk, {Connie M.} and Dominique L{\'e}vesque and Boisvert, {Fran{\c c}ois Michel} and Sheldon, {Ryan D.} and Rothbart, {Scott B.} and Crawford, {Peter A.} and Jones, {Russell G.}",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
doi = "10.1016/j.immuni.2023.07.002",
language = "English",
volume = "56",
pages = "2021--2035.e8",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "9",

}

RIS

TY - JOUR

T1 - Ketolysis drives CD8+ T cell effector function through effects on histone acetylation

AU - Luda, Katarzyna M.

AU - Longo, Joseph

AU - Kitchen-Goosen, Susan M.

AU - Duimstra, Lauren R.

AU - Ma, Eric H.

AU - Watson, McLane J.

AU - Oswald, Brandon M.

AU - Fu, Zhen

AU - Madaj, Zachary

AU - Kupai, Ariana

AU - Dickson, Bradley M.

AU - DeCamp, Lisa M.

AU - Dahabieh, Michael S.

AU - Compton, Shelby E.

AU - Teis, Robert

AU - Kaymak, Irem

AU - Lau, Kin H.

AU - Kelly, Daniel P.

AU - Puchalska, Patrycja

AU - Williams, Kelsey S.

AU - Krawczyk, Connie M.

AU - Lévesque, Dominique

AU - Boisvert, François Michel

AU - Sheldon, Ryan D.

AU - Rothbart, Scott B.

AU - Crawford, Peter A.

AU - Jones, Russell G.

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies (KBs)—including β-hydroxybutyrate (βOHB) and acetoacetate (AcAc)—as essential fuels supporting CD8+ T cell metabolism and effector function. βOHB directly increased CD8+ T effector (Teff) cell cytokine production and cytolytic activity, and KB oxidation (ketolysis) was required for Teff cell responses to bacterial infection and tumor challenge. CD8+ Teff cells preferentially used KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boosted the respiratory capacity and TCA cycle-dependent metabolic pathways that fuel CD8+ T cell function. Mechanistically, βOHB was a major substrate for acetyl-CoA production in CD8+ T cells and regulated effector responses through effects on histone acetylation. Together, our results identify cell-intrinsic ketolysis as a metabolic and epigenetic driver of optimal CD8+ T cell effector responses.

AB - Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies (KBs)—including β-hydroxybutyrate (βOHB) and acetoacetate (AcAc)—as essential fuels supporting CD8+ T cell metabolism and effector function. βOHB directly increased CD8+ T effector (Teff) cell cytokine production and cytolytic activity, and KB oxidation (ketolysis) was required for Teff cell responses to bacterial infection and tumor challenge. CD8+ Teff cells preferentially used KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boosted the respiratory capacity and TCA cycle-dependent metabolic pathways that fuel CD8+ T cell function. Mechanistically, βOHB was a major substrate for acetyl-CoA production in CD8+ T cells and regulated effector responses through effects on histone acetylation. Together, our results identify cell-intrinsic ketolysis as a metabolic and epigenetic driver of optimal CD8+ T cell effector responses.

KW - acetyl-CoA

KW - cancer immunology

KW - CD8 T cells

KW - effector function

KW - epigenetics

KW - ketolysis

KW - ketone bodies

KW - metabolism

KW - TCA cycle

U2 - 10.1016/j.immuni.2023.07.002

DO - 10.1016/j.immuni.2023.07.002

M3 - Journal article

C2 - 37516105

AN - SCOPUS:85169013765

VL - 56

SP - 2021-2035.e8

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 9

ER -

ID: 366763950