Activation-specific metabolic requirements for NK Cell IFN-γ production.
Activation-specific metabolic requirements for NK Cell IFN-γ production.
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DOI：
10.4049/jimmunol.1402099
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发表时间：
2015-02-15
期刊：
影响因子：
--
通讯作者：
Cooper MA
中科院分区：
文献类型：
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作者：
Keppel MP;Saucier N;Mah AY;Vogel TP;Cooper MA
There has been increasing recognition of the importance of cellular metabolism and metabolic substrates for the function and differentiation of immune cells. Here, for the first time, we investigate the metabolic requirements for production of IFN-γ by freshly isolated NK cells. Primary murine NK cells mainly utilize mitochondrial oxidative phosphorylation at rest and with short-term activation. Remarkably, we discovered significant differences in the metabolic requirements of murine NK cell IFN-γ production depending upon the activation signal. Stimulation of NK cell IFN-γ production was independent of glycolysis or mitochondrial oxidative phosphorylation when cells were activated with IL-12+IL-18. By contrast, stimulation via activating NK receptors required glucose-driven oxidative phosphorylation. Prolonged treatment with high-dose, but not low dose, IL-15 eliminated the metabolic requirement for receptor stimulation. In summary, this study demonstrates that metabolism provides an essential second signal for induction of IFN-γ production by activating NK cell receptors that can be reversed with prolonged high-dose IL-15 treatment.
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