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

Nadine Assmann, Katie L. O'Brien, Raymond P. Donnelly, Lydia Dyck, Vanessa Zaiatz-Bittencourt, Róisín M. Loftus, Paul Heinrich, Peter J. Oefner, Lydia Lynch, Clair M. Gardiner, Katja Dettmer, David K. Finlay

Research output: Contribution to journalArticlepeer-review

243 Scopus citations

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-3 and NK cell cytotoxicity. Thus, Srebp controls glucose metabolism in NK cells, and this Srebp-dependent regulation is critical for NK cell effector function.

Original languageEnglish (US)
Pages (from-to)1197-1206
Number of pages10
JournalNature Immunology
Volume18
Issue number11
DOIs
StatePublished - Oct 18 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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