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

Roger Geiger; Jan C Rieckmann; Tobias Wolf; Camilla Basso; Yuehan Feng; Tobias Fuhrer; Maria Kogadeeva; Paola Picotti; Felix Meissner; Matthias Mann; Nicola Zamboni; Federica Sallusto; Antonio Lanzavecchia

doi:10.1016/j.cell.2016.09.031

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

Roger Geiger, Jan C Rieckmann, Tobias Wolf, Camilla Basso, Yuehan Feng, Tobias Fuhrer, Maria Kogadeeva, Paola Picotti, Felix Meissner, Matthias Mann, Nicola Zamboni, Federica Sallusto, Antonio Lanzavecchia

433 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Cell
Vol/bind	167
Udgave nummer	3
Sider (fra-til)	829-842.e13
ISSN	0092-8674
DOI	https://doi.org/10.1016/j.cell.2016.09.031
Status	Udgivet - 20 okt. 2016
Udgivet eksternt	Ja

Adgang til dokumentet

10.1016/j.cell.2016.09.031

http://www.cell.com/article/S0092867416313137/pdfLicens: CC BY-NC-ND

Citationsformater

@article{dfb474fedd0c4518ab7c8fdd23a578cb,

title = "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 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.",

keywords = "Adaptor Proteins, Signal Transducing, Animals, Arginine, CD4-Positive T-Lymphocytes, DNA-Binding Proteins, Gene Knockout Techniques, Glycolysis, Humans, Immunologic Memory, Immunomodulation, Lymphocyte Activation, Melanoma, Experimental, Metabolome, Mice, Mice, Inbred BALB C, Oxidative Phosphorylation, Proteome, Skin Neoplasms, Transcription Factors, Transcription, Genetic, Journal Article, Research Support, Non-U.S. Gov't",

author = "Roger Geiger and Rieckmann, {Jan C} and Tobias Wolf and Camilla Basso and Yuehan Feng and Tobias Fuhrer and Maria Kogadeeva and Paola Picotti and Felix Meissner and Matthias Mann and Nicola Zamboni and Federica Sallusto and Antonio Lanzavecchia",

year = "2016",

month = oct,

day = "20",

doi = "10.1016/j.cell.2016.09.031",

language = "English",

volume = "167",

pages = "829--842.e13",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "3",

}

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

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

SN - 0092-8674

VL - 167

SP - 829-842.e13

JO - Cell

JF - Cell

IS - 3

ER -

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

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater