GOT1 调控 CD8 效应器和记忆 T 细胞的生成。
GOT1 regulates CD8 effector and memory T cell generation.
机构信息
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Calico LLC, South San Francisco, CA 94080, USA.
出版信息
Cell Rep. 2023 Jan 31;42(1):111987. doi: 10.1016/j.celrep.2022.111987. Epub 2023 Jan 12.
T cell activation, proliferation, function, and differentiation are tightly linked to proper metabolic reprogramming and regulation. By using [U-C]glucose tracing, we reveal a critical role for GOT1 in promoting CD8 T cell effector differentiation and function. Mechanistically, GOT1 enhances proliferation by maintaining intracellular redox balance and serine-mediated purine nucleotide biosynthesis. Further, GOT1 promotes the glycolytic programming and cytotoxic function of cytotoxic T lymphocytes via posttranslational regulation of HIF protein, potentially by regulating the levels of α-ketoglutarate. Conversely, genetic deletion of GOT1 promotes the generation of memory CD8 T cells.
T 细胞的激活、增殖、功能和分化与适当的代谢重编程和调节密切相关。通过使用 [U-C]葡萄糖示踪，我们揭示了 GOT1 在促进 CD8 T 细胞效应器分化和功能中的关键作用。从机制上讲，GOT1 通过维持细胞内氧化还原平衡和丝氨酸介导的嘌呤核苷酸生物合成来促进增殖。此外，GOT1 通过翻译后调节 HIF 蛋白，可能通过调节 α-酮戊二酸的水平，促进细胞毒性 T 淋巴细胞的糖酵解编程和细胞毒性功能。相反，GOT1 的基因缺失促进了记忆性 CD8 T 细胞的产生。
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