L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Cell |
Volume | 167 |
Issue number | 3 |
Pages (from-to) | 829-842.e13 |
ISSN | 0092-8674 |
DOIs | |
Publication status | Published - 20 Oct 2016 |
Externally published | Yes |
- Adaptor Proteins, Signal Transducing, Animals, Arginine, CD4-Positive T-Lymphocytes, DNA-Binding Proteins, Gene Knockout Techniques, Glycolysis, Humans, Immunologic Memory, Immunomodulation, Lymphocyte Activation, Melanoma, Experimental, Metabolome, Mice, Mice, Inbred BALB C, Oxidative Phosphorylation, Proteome, Skin Neoplasms, Transcription Factors, Transcription, Genetic, Journal Article, Research Support, Non-U.S. Gov't
Research areas
ID: 184324395