NKT cells adopt a glutamine-addicted phenotype to regulate their homeostasis and function.
NKT cells adopt a glutamine-addicted phenotype to regulate their homeostasis and function.
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DOI：
10.1016/j.celrep.2022.111516
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发表时间：
2022-10-25
期刊：
影响因子：
8.8
通讯作者：
Chang, Cheong-Hee
中科院分区：
文献类型：
--
作者：
Kumar, Ajay;Yarosz, Emily L.;Andren, Anthony;Zhang, Li;Lyssiotis, Costas A.;Chang, Cheong-Hee
自然杀伤T（NKT）细胞与CD 4 T细胞的代谢程序明显不同，包括对谷氨酰胺的严格要求以调节细胞稳态。然而，其潜在机制仍不清楚。在这里，我们报告说，在稳定状态下，NKT细胞具有比CD 4 T细胞更高的谷氨酰胺水平，并且NKT细胞在活化时增加了谷氨酰胺分解。活化的NKT细胞使用谷氨酰胺来为三羧酸循环和谷胱甘肽合成提供燃料。此外，谷氨酰胺衍生的氮能够通过己糖胺生物合成途径（HBP）实现蛋白质糖基化。谷氨酰胺代谢的每个分支似乎对NKT细胞稳态和线粒体功能至关重要。谷氨酰胺分解和HBP差异调节白细胞介素-4（IL-4）和干扰素γ（IFNγ）的产生。谷氨酰胺代谢似乎是由AMP激活的蛋白激酶（AMPK）-雷帕霉素复合物1（mTORC 1）信号转导的哺乳动物目标控制。这些发现强调了与CD 4 T细胞相比，NKT细胞的独特代谢需求，这可能在某些营养限制性疾病的治疗中具有治疗意义。Kumar等人报道NKT细胞依赖谷氨酰胺来维持其稳态和功能。谷氨酰胺通过支持线粒体功能、维持氧化还原平衡和支持NKT细胞中的糖基化过程来实现这一点。
Natural killer T (NKT) cells operate distinctly different metabolic programming from CD4 T cells, including a strict requirement for glutamine to regulate cell homeostasis. However, the underlying mechanisms remain unknown. Here, we report that at a steady state, NKT cells have higher glutamine levels than CD4 T cells and that NKT cells increase glutaminolysis on activation. Activated NKT cells use glutamine to fuel the tricarboxylic acid cycle and glutathione synthesis. In addition, glutamine-derived nitrogen enables protein glycosylation via the hexosamine biosynthesis pathway (HBP). Each of these branches of glutamine metabolism seems to be critical for NKT cell homeostasis and mitochondrial functions. Glutaminolysis and HBP differentially regulate interleukin-4 (IL-4) and interferon γ (IFNγ) production. Glutamine metabolism appears to be controlled by AMP-activated protein kinase (AMPK)-mammalian target of rapamycin complex 1 (mTORC1) signaling. These findings highlight a distinct metabolic requirement of NKT cells compared with CD4 T cells, which may have therapeutic implications in the treatment of certain nutrient-restricted diseases. Kumar et al. report that NKT cells rely on glutamine for their homeostasis and functions. Glutamine does this by supporting mitochondrial functions, maintaining redox balance, and supporting glycosylation processes in NKT cells.
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影响因子：
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作者：
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