Carbon source availability drives nutrient utilization in CD8+ T cells

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

Standard

Carbon source availability drives nutrient utilization in CD8+ T cells. / Kaymak, Irem; Luda, Katarzyna M.; Duimstra, Lauren R.; Ma, Eric H.; Longo, Joseph; Dahabieh, Michael S.; Faubert, Brandon; Oswald, Brandon M.; Watson, McLane J.; Kitchen-Goosen, Susan M.; DeCamp, Lisa M.; Compton, Shelby E.; Fu, Zhen; DeBerardinis, Ralph J.; Williams, Kelsey S.; Sheldon, Ryan D.; Jones, Russell G.

In: Cell Metabolism, Vol. 34, No. 9, 2022, p. 1298-1311.

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

Harvard

Kaymak, I, Luda, KM, Duimstra, LR, Ma, EH, Longo, J, Dahabieh, MS, Faubert, B, Oswald, BM, Watson, MJ, Kitchen-Goosen, SM, DeCamp, LM, Compton, SE, Fu, Z, DeBerardinis, RJ, Williams, KS, Sheldon, RD & Jones, RG 2022, 'Carbon source availability drives nutrient utilization in CD8+ T cells', Cell Metabolism, vol. 34, no. 9, pp. 1298-1311. https://doi.org/10.1016/j.cmet.2022.07.012

APA

Kaymak, I., Luda, K. M., Duimstra, L. R., Ma, E. H., Longo, J., Dahabieh, M. S., Faubert, B., Oswald, B. M., Watson, M. J., Kitchen-Goosen, S. M., DeCamp, L. M., Compton, S. E., Fu, Z., DeBerardinis, R. J., Williams, K. S., Sheldon, R. D., & Jones, R. G. (2022). Carbon source availability drives nutrient utilization in CD8+ T cells. Cell Metabolism, 34(9), 1298-1311. https://doi.org/10.1016/j.cmet.2022.07.012

Vancouver

Kaymak I, Luda KM, Duimstra LR, Ma EH, Longo J, Dahabieh MS et al. Carbon source availability drives nutrient utilization in CD8+ T cells. Cell Metabolism. 2022;34(9):1298-1311. https://doi.org/10.1016/j.cmet.2022.07.012

Author

Kaymak, Irem ; Luda, Katarzyna M. ; Duimstra, Lauren R. ; Ma, Eric H. ; Longo, Joseph ; Dahabieh, Michael S. ; Faubert, Brandon ; Oswald, Brandon M. ; Watson, McLane J. ; Kitchen-Goosen, Susan M. ; DeCamp, Lisa M. ; Compton, Shelby E. ; Fu, Zhen ; DeBerardinis, Ralph J. ; Williams, Kelsey S. ; Sheldon, Ryan D. ; Jones, Russell G. / Carbon source availability drives nutrient utilization in CD8+ T cells. In: Cell Metabolism. 2022 ; Vol. 34, No. 9. pp. 1298-1311.

Bibtex

@article{cfed88a3de14457b91f9907610f2f792,
title = "Carbon source availability drives nutrient utilization in CD8+ T cells",
abstract = "How environmental nutrient availability impacts T cell metabolism and function remains poorly understood. Here, we report that the presence of physiologic carbon sources (PCSs) in cell culture medium broadly impacts glucose utilization by CD8+ T cells, independent of transcriptional changes in metabolic reprogramming. The presence of PCSs reduced glucose contribution to the TCA cycle and increased effector function of CD8+ T cells, with lactate directly fueling the TCA cycle. In fact, CD8+ T cells responding to Listeria infection preferentially consumed lactate over glucose as a TCA cycle substrate in vitro, with lactate enhancing T cell bioenergetic and biosynthetic capacity. Inhibiting lactate-dependent metabolism in CD8+ T cells by silencing lactate dehydrogenase A (Ldha) impaired both T cell metabolic homeostasis and proliferative expansion in vivo. Together, our data indicate that carbon source availability shapes T cell glucose metabolism and identifies lactate as a bioenergetic and biosynthetic fuel for CD8+ effector T cells.",
keywords = "(13)C tracing, immunometabolism, lactate, metabolic programming, metabolomics, T cells, TCA cycle",
author = "Irem Kaymak and Luda, {Katarzyna M.} and Duimstra, {Lauren R.} and Ma, {Eric H.} and Joseph Longo and Dahabieh, {Michael S.} and Brandon Faubert and Oswald, {Brandon M.} and Watson, {McLane J.} and Kitchen-Goosen, {Susan M.} and DeCamp, {Lisa M.} and Compton, {Shelby E.} and Zhen Fu and DeBerardinis, {Ralph J.} and Williams, {Kelsey S.} and Sheldon, {Ryan D.} and Jones, {Russell G.}",
note = "Publisher Copyright: Copyright {\textcopyright} 2022 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2022",
doi = "10.1016/j.cmet.2022.07.012",
language = "English",
volume = "34",
pages = "1298--1311",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "9",

}

RIS

TY - JOUR

T1 - Carbon source availability drives nutrient utilization in CD8+ T cells

AU - Kaymak, Irem

AU - Luda, Katarzyna M.

AU - Duimstra, Lauren R.

AU - Ma, Eric H.

AU - Longo, Joseph

AU - Dahabieh, Michael S.

AU - Faubert, Brandon

AU - Oswald, Brandon M.

AU - Watson, McLane J.

AU - Kitchen-Goosen, Susan M.

AU - DeCamp, Lisa M.

AU - Compton, Shelby E.

AU - Fu, Zhen

AU - DeBerardinis, Ralph J.

AU - Williams, Kelsey S.

AU - Sheldon, Ryan D.

AU - Jones, Russell G.

N1 - Publisher Copyright: Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2022

Y1 - 2022

N2 - How environmental nutrient availability impacts T cell metabolism and function remains poorly understood. Here, we report that the presence of physiologic carbon sources (PCSs) in cell culture medium broadly impacts glucose utilization by CD8+ T cells, independent of transcriptional changes in metabolic reprogramming. The presence of PCSs reduced glucose contribution to the TCA cycle and increased effector function of CD8+ T cells, with lactate directly fueling the TCA cycle. In fact, CD8+ T cells responding to Listeria infection preferentially consumed lactate over glucose as a TCA cycle substrate in vitro, with lactate enhancing T cell bioenergetic and biosynthetic capacity. Inhibiting lactate-dependent metabolism in CD8+ T cells by silencing lactate dehydrogenase A (Ldha) impaired both T cell metabolic homeostasis and proliferative expansion in vivo. Together, our data indicate that carbon source availability shapes T cell glucose metabolism and identifies lactate as a bioenergetic and biosynthetic fuel for CD8+ effector T cells.

AB - How environmental nutrient availability impacts T cell metabolism and function remains poorly understood. Here, we report that the presence of physiologic carbon sources (PCSs) in cell culture medium broadly impacts glucose utilization by CD8+ T cells, independent of transcriptional changes in metabolic reprogramming. The presence of PCSs reduced glucose contribution to the TCA cycle and increased effector function of CD8+ T cells, with lactate directly fueling the TCA cycle. In fact, CD8+ T cells responding to Listeria infection preferentially consumed lactate over glucose as a TCA cycle substrate in vitro, with lactate enhancing T cell bioenergetic and biosynthetic capacity. Inhibiting lactate-dependent metabolism in CD8+ T cells by silencing lactate dehydrogenase A (Ldha) impaired both T cell metabolic homeostasis and proliferative expansion in vivo. Together, our data indicate that carbon source availability shapes T cell glucose metabolism and identifies lactate as a bioenergetic and biosynthetic fuel for CD8+ effector T cells.

KW - (13)C tracing

KW - immunometabolism

KW - lactate

KW - metabolic programming

KW - metabolomics

KW - T cells

KW - TCA cycle

U2 - 10.1016/j.cmet.2022.07.012

DO - 10.1016/j.cmet.2022.07.012

M3 - Journal article

C2 - 35981545

AN - SCOPUS:85138125761

VL - 34

SP - 1298

EP - 1311

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 9

ER -

ID: 321473269