生物
精氨酸
代谢组
细胞内
糖酵解
细胞生物学
蛋白质组
新陈代谢
细胞
氧化磷酸化
生物化学
氨基酸
代谢物
作者
Roger Geiger,Jan C. Rieckmann,Tobias Wolf,Camilla Basso,Yuehan Feng,Tobias Fuhrer,Maria Kogadeeva,Paola Picotti,Felix Meissner,Matthias Mann,Nicola Zamboni,Federica Sallusto,Antonio Lanzavecchia
出处
期刊:Cell
[Elsevier]
日期:2016-10-01
卷期号:167 (3): 829-842.e13
被引量:1024
标识
DOI:10.1016/j.cell.2016.09.031
摘要
Metabolic activity is intimately linked to T cell fate and function. Using high-resolution mass spectrometry, we generated dynamic metabolome and proteome profiles of human primary naive T cells following activation. We discovered critical changes in the arginine metabolism that led to a drop in intracellular L-arginine concentration. Elevating L-arginine levels induced global metabolic changes including a shift from glycolysis to oxidative phosphorylation in activated T cells and promoted the generation of central memory-like cells endowed with higher survival capacity and, in a mouse model, anti-tumor activity. Proteome-wide probing of structural alterations, validated by the analysis of knockout T cell clones, identified three transcriptional regulators (BAZ1B, PSIP1, and TSN) that sensed L-arginine levels and promoted T cell survival. Thus, intracellular L-arginine concentrations directly impact the metabolic fitness and survival capacity of T cells that are crucial for anti-tumor responses.
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