Assmann, Nadine and O'Brien, Katie L. and Donnelly, Raymond P. and Dyck, Lydia and Zaiatz-Bittencourt, Vanessa and Loftus, Roisin M. and Heinrich, Paul and Oefner, Peter J. and Lynch, Lydia and Gardiner, Clair M. and Dettmer, Katja and Finlay, David K. (2017) Srebp-controlled glucose metabolism is essential for NK cell functional responses. NATURE IMMUNOLOGY, 18 (11). 1197-+. ISSN 1529-2908, 1529-2916
Full text not available from this repository. (Request a copy)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 cytokineinduced 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-gamma and NK cell cytotoxicity. Thus, Srebp controls glucose metabolism in NK cells, and this Srebp-dependent regulation is critical for NK cell effector function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NATURAL-KILLER-CELLS; ELEMENT-BINDING PROTEINS; FATTY-ACID SYNTHESIS; T-CELLS; EFFECTOR FUNCTION; LIPID-SYNTHESIS; METHYL-ESTERS; ACTIVATION; MEMORY; GENE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 25 Feb 2019 15:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1964 |
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