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Srebp-controlled glucose metabolism is essential for NK cell functional responses
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Journal Article
Srebp-controlled glucose metabolism is essential for NK cell functional responses
2017
Overview
NK cells are cytotoxic cells that combat tumors and viral infection. Finlay and colleagues show that the effector function of cytokine-activated NK cells depends on glucose metabolism via the citrate–malate shuttle that requires the metabolic regulator Srebp.
Activated natural killer (NK) cells engage in a robust metabolic response that is required for normal effector function. Using genetic, pharmacological and metabolic analyses, we demonstrated an essential role for Srebp transcription factors in cytokine-induced metabolic reprogramming of NK cells that was independent of their conventional role in the control of lipid synthesis. Srebp was required for elevated glycolysis and oxidative phosphorylation and promoted a distinct metabolic pathway configuration in which glucose was metabolized to cytosolic citrate via the citrate–malate shuttle. Preventing the activation of Srebp or direct inhibition of the citrate–malate shuttle inhibited production of interferon-γ and NK cell cytotoxicity. Thus, Srebp controls glucose metabolism in NK cells, and this Srebp-dependent regulation is critical for NK cell effector function.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 13/106
/ 13/31
/ 13/95
/ 38/77
/ 64/110
/ Animals
/ Glucose
/ Humans
/ Killer Cells, Natural - immunology
/ Killer Cells, Natural - metabolism
/ Sterol Regulatory Element Binding Protein 1 - metabolism
/ Sterol Regulatory Element Binding Protein 2 - metabolism
/ Sterol regulatory element-binding protein
/ T-Lymphocyte Subsets - immunology
