Cited by 375Immune Cell Function and InteractionImmune cells in cancerMetabolism, Diabetes, and Cancer

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

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Assmann, Nadine, O'Brien, Katie L, Donnelly, Raymond P, Dyck, Lydia, Zaiatz-Bittencourt, Vanessa, Loftus, Róisín M, Heinrich, Paul, Oefner, Peter J, Lynch, Lydia, Gardiner, Clair M, Dettmer, Katja, Finlay, David K·2017·Nature Immunology

DOI 10.1038/ni.3838

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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.

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Authors: Assmann, N., O'Brien, K. L., Donnelly, R. P., Dyck, L., Zaiatz-Bittencourt, V., Loftus, R. M., Heinrich, P., Oefner, P. J., Lynch, L., Gardiner, C. M., Dettmer, K., & Finlay, D. K.
Affiliations: Trinity College Dublin (IE)
University of Regensburg (DE)
Corresponding author: Finlay, David K
ORCID: Assmann, Nadine
Dyck, Lydia
Zaiatz-Bittencourt, Vanessa
Loftus, Róisín M
Oefner, Peter J
Lynch, Lydia
Gardiner, Clair M
Dettmer, Katja
Finlay, David K
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2017-09-18
Volume: 18
Issue: 11
Pages: 1197-1206
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni.3838
OpenAlex: W2755907400
Cited by: 375
References: 57
Citations by year: 2026: 35 · 2025: 54 · 2024: 37 · 2023: 44 · 2022: 53 · 2021: 57 · 2020: 45 · 2019: 25 · 2018: 21 · 2017: 4
FWCI: 11.74
Type: journal article
Language: en
Open access: green
zenodo.org
Licence: other-oa
www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: natural killer cells, SREBP, glucose metabolism, metabolic reprogramming, glycolysis, oxidative phosphorylation, interferon-gamma, NK cell cytotoxicity, cytokine activation, antitumor immunity, viral infection
MeSH terms: Animals, Flow Cytometry, Glucose, Glycolysis, Humans, Killer Cells, Natural, Lipids, Oxidative Phosphorylation, Immunoblotting, T-Lymphocyte Subsets, Cytokines, Cell Proliferation, Sterol Regulatory Element Binding Protein 1, Sterol Regulatory Element Binding Protein 2

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

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