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Nat Immunol. 2017 Nov;18(11):1197-1206. doi: 10.1038/ni.3838. Epub 2017 Sep 18.

Srebp-controlled glucose metabolism is essential for NK cell functional responses.

Author information

1
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
2
Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
3
School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.

Abstract

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.

PMID:
28920951
DOI:
10.1038/ni.3838
[Indexed for MEDLINE]

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