Enhanced oxidative phosphorylation in NKT cells is essential for their survival and function
Enhanced oxidative phosphorylation in NKT cells is essential for their survival and function
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DOI：
10.1073/pnas.1901376116
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发表时间：
2019-04-09
影响因子：
11.1
通讯作者：
Chang, Cheong-Hee
中科院分区：
文献类型：
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作者：
Kumar, Ajay;Pyaram, Kalyani;Chang, Cheong-Hee
细胞代谢和信号通路是决定传统T细胞命运和功能的关键调节因子，但对细胞代谢在自然杀伤T（NKT）细胞存活、增殖和功能中的作用知之甚少。我们发现NKT细胞与CD 4 T细胞进行不同的代谢编程。NKT细胞在葡萄糖摄取方面的效率低于活化或未活化的CD 4 T细胞。基因表达数据显示，在NKT细胞中，葡萄糖优先通过戊糖磷酸途径和线粒体代谢，而不是转化为乳酸。事实上，葡萄糖对于NKT细胞的效应子功能是必需的，并且高乳酸环境对于NKT细胞存活和增殖是有害的。NKT细胞中增加的葡萄糖摄取和IFN-γ表达与响应细菌感染的细菌负荷负相关，进一步支持葡萄糖代谢对NKT细胞功能的重要性。我们还发现早幼粒细胞白血病锌指蛋白可能在调节NKT细胞糖代谢中起作用。总的来说，我们的研究表明，NKT细胞使用不同的葡萄糖代谢臂来维持其生存和功能。
Cellular metabolism and signaling pathways are key regulators to determine conventional T cell fate and function, but little is understood about the role of cell metabolism for natural killer T (NKT) cell survival, proliferation, and function. We found that NKT cells operate distinct metabolic programming from CD4 T cells. NKT cells are less efficient in glucose uptake than CD4 T cells with or without activation. Gene-expression data revealed that, in NKT cells, glucose is preferentially metabolized by the pentose phosphate pathway and mitochondria, as opposed to being converted into lactate. In fact, glucose is essential for the effector functions of NKT cells and a high lactate environment is detrimental for NKT cell survival and proliferation. Increased glucose uptake and IFN-gamma expression in NKT cells is inversely correlated with bacterial loads in response to bacterial infection, further supporting the significance of glucose metabolism for NKT cell function. We also found that promyelocytic leukemia zinc finger seemed to play a role in regulating NKT cells' glucose metabolism. Overall, our study reveals that NKT cells use distinct arms of glucose metabolism for their survival and function.