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 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.
journal_name
Celljournal_title
Cellauthors
Geiger R,Rieckmann JC,Wolf T,Basso C,Feng Y,Fuhrer T,Kogadeeva M,Picotti P,Meissner F,Mann M,Zamboni N,Sallusto F,Lanzavecchia Adoi
10.1016/j.cell.2016.09.031subject
Has Abstractpub_date
2016-10-20 00:00:00pages
829-842.e13issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(16)31313-7journal_volume
167pub_type
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