<br>ATF4-SLC7A11-GSH 轴介导低精氨酸条件下激活的 CD4+ T 细胞获得免疫抑制特性,Cell Reports

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ATF4-SLC7A11-GSH 轴介导低精氨酸条件下激活的 CD4+ T 细胞获得免疫抑制特性
Cell Reports ( IF 7.5 ) Pub Date : 2024-03-23 , DOI: 10.1016/j.celrep.2024.113995
Ziqi Zou ₁ , Qian Cheng ₂ , Jiajie Zhou ₁ , Chenyao Guo ₁ , Andreas V Hadjinicolaou ₃ , Mariolina Salio ₄ , Xinghua Liang ₅ , Cuiyu Yang ₆ , Yue Du ₁ , Weiran Yao ₁ , Dongrui Wang ₅ , Vincenzo Cerundolo ₄ , Qingqing Wang ₇ , Meng Xia ₈

Affiliation

Institute of Immunology, and Department of Dermatology and Venereology of the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
MRC Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, UK.
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, UK; Early Cancer Institute, Department of Oncology, Hutchison Research Centre, University of Cambridge, CB2 0XZ Cambridge, UK.
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, UK.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311121, China.
Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Institute of Immunology, and Department of Dermatology and Venereology of the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311121, China.
Institute of Immunology, and Department of Dermatology and Venereology of the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, UK.

肿瘤微环境（TME）的代谢营养物质（包括半必需氨基酸精氨酸）受到限制。虽然完全剥夺精氨酸会导致 T 细胞功能障碍，但目前尚不清楚 TME 中精氨酸水平的波动如何影响 T 细胞的命运。在这里，我们发现 20 μM 低精氨酸条件（代表癌症患者血浆中的水平）赋予激活的 T 细胞类似 Treg 的免疫抑制能力。体内小鼠肿瘤模型和人类单细胞 RNA 测序数据集揭示了低精氨酸条件与肿瘤内 Treg 积累之间的正相关性。从机制上讲，低精氨酸激活的 T 细胞利用 ATF4-SLC7A11-GSH 轴进行代谢和转录重编程，以保留其抑制功能。这些发现提高了我们对精氨酸在人类 T 细胞生物学中的作用的理解，并具有免疫治疗策略的潜在应用。

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更新日期：2024-03-23

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