Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Bioprocessing Technology Institute, ASTAR (Agency for Science, Technology and Research), Singapore, Singapore.
Front Immunol. 2021 Feb 23;12:619195. doi: 10.3389/fimmu.2021.619195. eCollection 2021.
Cell metabolism plays a pivotal role in regulating the effector functions of immune cells. Stimulatory cytokines, such as interleukin (IL)-2 or IL-12 and IL-15, activate glycolysis and oxidative phosphorylation in natural killer (NK) cells to support their enhanced effector functions. IL-10, a pleiotropic cytokine, is known to suppress macrophage activation but stimulate NK cells. However, it remains unclear if IL-10 has an effect on the metabolism of human NK cells and if so, what metabolic mechanisms are affected, and how these metabolic changes are regulated and contribute to the effector functions of NK cells. In this study, we demonstrate that IL-10 upregulates both glycolysis and oxidative phosphorylation in human NK cells, and these metabolic changes are crucial for the enhanced effector functions of NK cells. Mechanistically, we unravel that IL-10 activates the mammalian target of rapamycin complex 1 (mTORC1) to regulate metabolic reprogramming in human NK cells.
细胞代谢在调节免疫细胞的效应功能方面起着关键作用。刺激细胞因子，如白细胞介素（IL）-2 或 IL-12 和 IL-15，激活自然杀伤（NK）细胞中的糖酵解和氧化磷酸化，以支持其增强的效应功能。白细胞介素 10（IL-10）是一种多效细胞因子，已知可抑制巨噬细胞激活，但可刺激 NK 细胞。然而，目前尚不清楚 IL-10 是否会影响人 NK 细胞的代谢，如果有影响，哪些代谢机制受到影响，以及这些代谢变化如何被调节并有助于 NK 细胞的效应功能。在这项研究中，我们证明了 IL-10 可上调人 NK 细胞中的糖酵解和氧化磷酸化，这些代谢变化对于增强 NK 细胞的效应功能至关重要。从机制上讲，我们揭示了 IL-10 通过激活雷帕霉素靶蛋白复合物 1（mTORC1）来调节人 NK 细胞中的代谢重编程。
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