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

Geiger, R., Rieckmann, J. C., Wolf, T., Basso, C., Feng, Y., Fuhrer, T., et al. (2016). L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. Cell, 167(3), 829-842. doi:10.1016/j.cell.2016.09.031.

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1-s2.0-S0092867416313137-main.pdf (Publisher version), 5MB
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2016 The Author(s). Published by Elsevier Inc. Open Access funded by European Research Council Under a Creative Commons license
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 Creators:
Geiger, Roger1, Author
Rieckmann, Jan C.2, Author              
Wolf, Tobias1, Author
Basso, Camilla1, Author
Feng, Yuehan1, Author
Fuhrer, Tobias1, Author
Kogadeeva, Maria1, Author
Picotti, Paola1, Author
Meissner, Felix3, Author              
Mann, Matthias2, Author              
Zamboni, Nicola1, Author
Sallusto, Federica1, Author
Lanzavecchia, Antonio1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
3Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149678              

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Free keywords: IN-VIVO; QUANTITATIVE PROTEOMICS; LYMPHOCYTE ACTIVATION; PROTEIN INTERACTIONS; MEMORY; EFFECTOR; GENE; ENRICHMENT; EXPRESSION; RESPONSESBiochemistry & Molecular Biology; Cell Biology;
 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 antitumor responses.

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Language(s): eng - English
 Dates: 2016-10-132016
 Publication Status: Published in print
 Pages: 27
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 Table of Contents: -
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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 167 (3) Sequence Number: - Start / End Page: 829 - 842 Identifier: ISSN: 0092-8674
CoNE: https://pure.mpg.de/cone/journals/resource/954925463183