13 C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8 + T cells.

Autor:	Ma EH; 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., DeCamp LM; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.; Metabolism and Nutrition (MeNu) Program, Van Andel Institute, Grand Rapids, MI, USA., Kaymak I; 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.; Metabolism and Nutrition (MeNu) Program, Van Andel Institute, Grand Rapids, MI, USA., Roy DG; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada., Verway MJ; Goodman Cancer Institute, Faculty of Medicine, McGill University, Montréal, QC, Canada., Johnson RM; Gilead Sciences, Inc., Foster City, CA, USA., Samborska B; Goodman Cancer Institute, Faculty of Medicine, McGill University, Montréal, QC, Canada., Scullion CA; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Steadman M; Agios Pharmaceuticals, Cambridge, MA, USA., Vos M; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.; Metabolism and Nutrition (MeNu) Program, Van Andel Institute, Grand Rapids, MI, USA., Roddy TP; Agios Pharmaceuticals, Cambridge, MA, USA., Krawczyk CM; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.; Metabolism and Nutrition (MeNu) Program, Van Andel Institute, Grand Rapids, MI, USA., Williams KS; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.; Metabolism and Nutrition (MeNu) Program, Van Andel Institute, Grand Rapids, MI, USA., Sheldon RD; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.; Metabolism and Nutrition (MeNu) Program, Van Andel Institute, Grand Rapids, MI, USA.; Mass Spectrometry Core, Van Andel Institute, Grand Rapids, MI, USA., Jones RG; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.; Metabolism and Nutrition (MeNu) Program, Van Andel Institute, Grand Rapids, MI, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Jun 11. Date of Electronic Publication: 2023 Jun 11.
DOI:	10.1101/2023.06.09.544407
Abstrakt:	Infusion of 13C-labeled metabolites provides a gold-standard for understanding the metabolic processes used by T cells during immune responses in vivo . Through infusion of 13C-labeled metabolites (glucose, glutamine, acetate) in Listeria monocytogenes ( Lm )-infected mice, we demonstrate that CD8+ T effector (Teff) cells utilize metabolites for specific pathways during specific phases of activation. Highly proliferative early Teff cells in vivo shunt glucose primarily towards nucleotide synthesis and leverage glutamine anaplerosis in the tricarboxylic acid (TCA) cycle to support ATP and de novo pyrimidine synthesis. Additionally, early Teff cells rely on glutamic-oxaloacetic transaminase 1 (Got1)-which regulates de novo aspartate synthesis-for effector cell expansion in vivo . Importantly, Teff cells change fuel preference over the course of infection, switching from glutamine- to acetate-dependent TCA cycle metabolism late in infection. This study provides insights into the dynamics of Teff metabolism, illuminating distinct pathways of fuel consumption associated with Teff cell function in vivo . Competing Interests: Competing interests: RGJ is a scientific advisor for Agios Pharmaceuticals and Servier Pharmaceuticals and is a member of the Scientific Advisory Board of Immunomet Therapeutics.
Databáze:	MEDLINE
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