ATF4-SLC7A11-GSH axis mediates the acquisition of immunosuppressive properties by activated CD4+ T cells in low arginine condition
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..
The tumor microenvironment (TME) is restricted in metabolic nutrients including the semi-essential amino acid arginine. While complete arginine deprivation causes T cell dysfunction, it remains unclear how arginine levels fluctuate in the TME to shape T cell fates. Here, we find that the 20-μM low arginine condition, representing the levels found in the plasma of patients with cancers, confers Treg-like immunosuppressive capacities upon activated T cells. In vivo mouse tumor models and human single-cell RNA-sequencing datasets reveal positive correlations between low arginine condition and intratumoral Treg accumulation. Mechanistically, low arginine-activated T cells engage in metabolic and transcriptional reprogramming, using the ATF4-SLC7A11-GSH axis, to preserve their suppressive function. These findings improve our understanding of the role of arginine in human T cell biology with potential applications for immunotherapy strategies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Cell reports - 43(2024), 4 vom: 23. Apr., Seite 113995 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zou, Ziqi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.04.2024 Date Revised 26.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2024.113995 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a The tumor microenvironment (TME) is restricted in metabolic nutrients including the semi-essential amino acid arginine. While complete arginine deprivation causes T cell dysfunction, it remains unclear how arginine levels fluctuate in the TME to shape T cell fates. Here, we find that the 20-μM low arginine condition, representing the levels found in the plasma of patients with cancers, confers Treg-like immunosuppressive capacities upon activated T cells. In vivo mouse tumor models and human single-cell RNA-sequencing datasets reveal positive correlations between low arginine condition and intratumoral Treg accumulation. Mechanistically, low arginine-activated T cells engage in metabolic and transcriptional reprogramming, using the ATF4-SLC7A11-GSH axis, to preserve their suppressive function. These findings improve our understanding of the role of arginine in human T cell biology with potential applications for immunotherapy strategies | ||
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| 700 | 1 | |a Cheng, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jiajie |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Chenyao |e verfasserin |4 aut | |
| 700 | 1 | |a Hadjinicolaou, Andreas V |e verfasserin |4 aut | |
| 700 | 1 | |a Salio, Mariolina |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Xinghua |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Cuiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Weiran |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Dongrui |e verfasserin |4 aut | |
| 700 | 1 | |a Cerundolo, Vincenzo |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qingqing |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Meng |e verfasserin |4 aut | |
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