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L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.
- Source :
-
Cell . Oct2016, Vol. 167 Issue 3, p829-842.e13. 1p. - Publication Year :
- 2016
-
Abstract
- Summary 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00928674
- Volume :
- 167
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 118898892
- Full Text :
- https://doi.org/10.1016/j.cell.2016.09.031