L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. / Geiger, Roger; Rieckmann, Jan C; Wolf, Tobias; Basso, Camilla; Feng, Yuehan; Fuhrer, Tobias; Kogadeeva, Maria; Picotti, Paola; Meissner, Felix; Mann, Matthias; Zamboni, Nicola; Sallusto, Federica; Lanzavecchia, Antonio.
I: Cell, Bind 167, Nr. 3, 20.10.2016, s. 829-842.e13.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity
AU - Geiger, Roger
AU - Rieckmann, Jan C
AU - Wolf, Tobias
AU - Basso, Camilla
AU - Feng, Yuehan
AU - Fuhrer, Tobias
AU - Kogadeeva, Maria
AU - Picotti, Paola
AU - Meissner, Felix
AU - Mann, Matthias
AU - Zamboni, Nicola
AU - Sallusto, Federica
AU - Lanzavecchia, Antonio
N1 - Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2016/10/20
Y1 - 2016/10/20
N2 - 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.
AB - 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.
KW - Adaptor Proteins, Signal Transducing
KW - Animals
KW - Arginine
KW - CD4-Positive T-Lymphocytes
KW - DNA-Binding Proteins
KW - Gene Knockout Techniques
KW - Glycolysis
KW - Humans
KW - Immunologic Memory
KW - Immunomodulation
KW - Lymphocyte Activation
KW - Melanoma, Experimental
KW - Metabolome
KW - Mice
KW - Mice, Inbred BALB C
KW - Oxidative Phosphorylation
KW - Proteome
KW - Skin Neoplasms
KW - Transcription Factors
KW - Transcription, Genetic
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.cell.2016.09.031
DO - 10.1016/j.cell.2016.09.031
M3 - Journal article
C2 - 27745970
VL - 167
SP - 829-842.e13
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -
ID: 184324395