The glucose transporter 2 regulates CD8+ T cell function via environment sensing
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Published:2023-10-26
Issue:11
Volume:5
Page:1969-1985
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ISSN:2522-5812
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Container-title:Nature Metabolism
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language:en
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Short-container-title:Nat Metab
Author:
Fu Hongmei, Vuononvirta Juho, Fanti Silvia, Bonacina FabriziaORCID, D’Amati AntonioORCID, Wang Guosu, Poobalasingam Thanushiyan, Fankhaenel MariaORCID, Lucchesi DavideORCID, Coleby Rachel, Tarussio David, Thorens BernardORCID, Hearnden Robert J.ORCID, Longhi M. Paula, Grevitt PaulORCID, Sheikh Madeeha H., Solito EgleORCID, Godinho Susana A.ORCID, Bombardieri Michele, Smith David M.ORCID, Cooper DianneORCID, Iqbal Asif J.ORCID, Rathmell Jeffrey C.ORCID, Schaefer Samuel, Morales ValleORCID, Bianchi Katiuscia, Norata Giuseppe DaniloORCID, Marelli-Berg Federica M.ORCID
Abstract
AbstractT cell activation is associated with a profound and rapid metabolic response to meet increased energy demands for cell division, differentiation and development of effector function. Glucose uptake and engagement of the glycolytic pathway are major checkpoints for this event. Here we show that the low-affinity, concentration-dependent glucose transporter 2 (Glut2) regulates the development of CD8+ T cell effector responses in mice by promoting glucose uptake, glycolysis and glucose storage. Expression of Glut2 is modulated by environmental factors including glucose and oxygen availability and extracellular acidification. Glut2 is highly expressed by circulating, recently primed T cells, allowing efficient glucose uptake and storage. In glucose-deprived inflammatory environments, Glut2 becomes downregulated, thus preventing passive loss of intracellular glucose. Mechanistically, Glut2 expression is regulated by a combination of molecular interactions involving hypoxia-inducible factor-1 alpha, galectin-9 and stomatin. Finally, we show that human T cells also rely on this glucose transporter, thus providing a potential target for therapeutic immunomodulation.
Funder
British Heart Foundation Cancer Research UK
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Physiology (medical),Endocrinology, Diabetes and Metabolism,Internal Medicine
Reference51 articles.
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