The glucose transporter GLUT3 controls T helper 17 cell responses through glycolytic-epigenetic reprogramming

Hochrein SM, Wu H, Eckstein M, Arrigoni L, Herman JS, Schumacher F, Gerecke C, Rosenfeldt M, Gru D, Kleuser B, Gasteiger G, Kastenmu W, Ghesquiere B, Van Den Bossche J, Abel ED, Vaeth M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cell Metabolism Elsevier (Cell Press)

Book Volume: 34

Pages Range: 516-532.e11

Journal Issue: 4

DOI: 10.1016/j.cmet.2022.02.015

Abstract

Metabolic reprogramming is a hallmark of activated T cells. The switch from oxidative phosphorylation to aerobic glycolysis provides energy and intermediary metabolites for the biosynthesis of macromolecules to support clonal expansion and effector function. Here, we show that glycolytic reprogramming additionally controls inflammatory gene expression via epigenetic remodeling. We found that the glucose transporter GLUT3 is essential for the effector functions of Th17 cells in models of autoimmune colitis and encephalomyelitis. At the molecular level, we show that GLUT3-dependent glucose uptake controls a metabolic-transcriptional circuit that regulates the pathogenicity of Th17 cells. Metabolomic, epigenetic, and transcriptomic analyses linked GLUT3 to mitochondrial glucose oxidation and ACLY-dependent acetyl-CoA generation as a rate-limiting step in the epigenetic regulation of inflammatory gene expression. Our findings are also important from a translational perspective because inhibiting GLUT3-dependent acetyl-CoA generation is a promising metabolic checkpoint to mitigate Th17-cell-mediated inflammatory diseases.

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) Freie Universität Berlin DE Germany (DE) Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics DE Germany (DE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) Vrije Universiteit Amsterdam (VU) / University Amsterdam NL Netherlands (NL) University of Iowa US United States (USA) (US)

How to cite

APA:

Hochrein, S.M., Wu, H., Eckstein, M., Arrigoni, L., Herman, J.S., Schumacher, F.,... Vaeth, M. (2022). The glucose transporter GLUT3 controls T helper 17 cell responses through glycolytic-epigenetic reprogramming. Cell Metabolism, 34(4), 516-532.e11. https://doi.org/10.1016/j.cmet.2022.02.015

MLA:

Hochrein, Sophia M., et al. "The glucose transporter GLUT3 controls T helper 17 cell responses through glycolytic-epigenetic reprogramming." Cell Metabolism 34.4 (2022): 516-532.e11.

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