L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.

ABSTRACT: 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 sens

SUBMITTER: Geiger R 

PROVIDER: S-EPMC5075284 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature