TY - JOUR
T1 - The glucose transporter 2 regulates CD8+ T cell function via environment sensing
AU - Fu, Hongmei
AU - Vuononvirta, Juho
AU - Fanti, Silvia
AU - Bonacina, Fabrizia
AU - D'Amati, Antonio
AU - Wang, Guosu
AU - Poobalasingam, Thanushiyan
AU - Fankhaenel, Maria
AU - Lucchesi, Davide
AU - Coleby, Rachel
AU - Tarussio, David
AU - Thorens, Bernard
AU - Hearnden, Robert J
AU - Longhi, M Paula
AU - Grevitt, Paul
AU - Sheikh, Madeeha H
AU - Solito, Egle
AU - Godinho, Susana A
AU - Bombardieri, Michele
AU - Smith, David M
AU - Cooper, Dianne
AU - Iqbal, Asif J
AU - Rathmell, Jeffrey C
AU - Schaefer, Samuel
AU - Morales, Valle
AU - Bianchi, Katiuscia
AU - Norata, Giuseppe Danilo
AU - Marelli-Berg, Federica M
N1 - Acknowledgements:
We acknowledge funding from the British Heart Foundation (RG/20/8/34995, CH/15/2/32064 and AA/18/5/34222; to F.M.M.-B.).
Copyright:
© 2023. The Author(s).
PY - 2023/10/26
Y1 - 2023/10/26
N2 - T 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.
AB - T 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.
U2 - 10.1038/s42255-023-00913-9
DO - 10.1038/s42255-023-00913-9
M3 - Article
C2 - 37884694
SN - 2522-5812
JO - Nature metabolism
JF - Nature metabolism
ER -