Carbon source availability drives nutrient utilization in CD8 + T cells.

Autor:	Kaymak I; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Luda KM; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA; University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Blegdamsvej 3B, 2200 København, Denmark., Duimstra LR; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Ma EH; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Longo J; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Dahabieh MS; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Faubert B; Department of Medicine-Hematology and Oncology, University of Chicago, Chicago, IL, USA., Oswald BM; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Watson MJ; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Kitchen-Goosen SM; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., DeCamp LM; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Compton SE; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Fu Z; Bioinformatics and Biostatistics Core Facility, Van Andel Institute, Grand Rapids, MI, USA., DeBerardinis RJ; Children's Medical Center Research Institute, University of Texas (UT) Southwestern Medical Center, Dallas, TX, USA; Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX, USA., Williams KS; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Sheldon RD; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA; Metabolomics and Bioenergetics Core Facility, Van Andel Institute, Grand Rapids, MI, USA., Jones RG; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA. Electronic address: russell.jones@vai.org.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2022 Sep 06; Vol. 34 (9), pp. 1298-1311.e6. Date of Electronic Publication: 2022 Aug 17.
DOI:	10.1016/j.cmet.2022.07.012
Abstrakt:	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. Competing Interests: Declaration of interests R.J.D. is a founder and consultant for Atavistik Biosciences and an advisor for Agios Pharmaceuticals, Nirogy Therapeutics, and Vida Ventures. R.G.J. is a scientific advisor for Agios Pharmaceuticals and Servier Pharmaceuticals and is a member of the Scientific Advisory Board of Immunomet Therapeutics. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu