13C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8+ T cells.
13C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8+ T cells.
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13C 代谢物追踪揭示谷氨酰胺和乙酸盐是 CD8 T 细胞的关键体内燃料。
DOI：
10.1101/2023.06.09.544407
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Williams,
中科院分区：
文献类型：
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作者：
Ma,EricH;Dahabieh,MichaelS;DeCamp,LisaM;Kaymak,Irem;Kitchen-Goosen,SusanM;Roy,DominicG;Verway,MarkJ;Johnson,RadiaM;Samborska,Bozena;Scullion,CatherineA;Steadman,Mya;Vos,Matthew;Roddy,ThomasP;Krawczyk,ConnieM;Williams,
输注13c标记的代谢物为理解T细胞在体内免疫应答过程中使用的代谢过程提供了金标准。通过在单核细胞增生李斯特菌感染的小鼠中输注13c标记的代谢物（葡萄糖、谷氨酰胺和醋酸盐），我们证明CD8 T效应（Teff）细胞在特定的激活阶段使用代谢物进行特定的途径。体内高度增殖的早期Teff细胞主要将葡萄糖分流到核苷酸合成，并利用三羧酸（TCA）循环中的谷氨酰胺逆转来支持三磷酸腺苷和从头合成嘧啶。此外，早期Teff细胞依靠谷草转氨酶1 （Got1）在体内进行效应细胞扩增，Got1调节从头合成天冬氨酸。CD8 Teff细胞在感染过程中改变燃料偏好，在感染后期从依赖谷氨酰胺转变为依赖醋酸酯的TCA循环代谢。这项研究提供了对Teff代谢动力学的见解，阐明了体内CD8 Teff细胞功能相关的不同燃料消耗途径。
Infusion of13C-labeled metabolites provides a gold standard for understanding the metabolic processes used by T cells during immune responses in vivo. Through infusion of13C-labeled metabolites (glucose, glutamine, and acetate) inListeria monocytogenes–infected mice, we demonstrate that CD8 T effector (Teff) cells use metabolites for specific pathways during specific phases of activation. Highly proliferative early Teff cells in vivo shunt glucose primarily toward nucleotide synthesis and leverage glutamine anaplerosis in the tricarboxylic acid (TCA) cycle to support adenosine triphosphate and de novo pyrimidine synthesis. In addition, early Teff cells rely on glutamic-oxaloacetic transaminase 1 (Got1)—which regulates de novo aspartate synthesis—for effector cell expansion in vivo. CD8 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 CD8 Teff cell function in vivo.