谷氨酰胺
体内
柠檬酸循环
生物
效应器
生物化学
代谢途径
新陈代谢
碳水化合物代谢
CD8型
细胞生物学
化学
免疫系统
氨基酸
免疫学
生物技术
作者
H. Eric,Michael Dahabieh,Lisa DeCamp,Irem Kaymak,Susan M. Kitchen-Goosen,Dominic G. Roy,Mark Verway,Radia Marie Johnson,Bożena Samborska,Catherine Scullion,Mya Steadman,Matthew Vos,Thomas P. Roddy,Connie M. Krawczyk,Kelsey S. Williams,Ryan D. Sheldon,Russell G. Jones
标识
DOI:10.1101/2023.06.09.544407
摘要
Abstract 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 . Teaser Interrogating dynamics of fuel utilization by CD8 + T cells in vivo reveals new metabolic checkpoints for immune function in vivo .
科研通智能强力驱动
Strongly Powered by AbleSci AI