期刊
CELL
卷 167, 期 3, 页码 829-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.09.031
关键词
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资金
- Swiss Vaccine Research Institute
- Swiss National Science Foundation [149475]
- European Research Council [323183 PREDICT]
- Swiss SystemsX.ch initiative
- Helmut Horten Foundation
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 antitumor responses.
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