Carbon source availability drives nutrient utilization in CD8+ T cells
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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
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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