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The glucose transporter 2 regulates CD8 + T cell function via environment sensing.

Hongmei FuJuho VuononvirtaSilvia FantiFabrizia BonacinaAntonio D'AmatiGuosu WangThanushiyan PoobalasingamMaria FankhaenelDavide LucchesiRachel ColebyDavid TarussioBernard ThorensRobert J HearndenM Paula LonghiPaul GrevittMadeeha H SheikhEgle SolitoSusana A GodinhoMichele BombardieriDavid M SmithDianne CooperAsif Jilani IqbalJeffrey C RathmellSamuel SchaeferValle MoralesKatiuscia BianchiGiuseppe Danilo NorataFederica M Marelli-Berg
Published in: Nature metabolism (2023)
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.
Keyphrases
  • blood glucose
  • stem cells
  • type diabetes
  • bone marrow
  • oxidative stress
  • blood pressure
  • social media
  • cell therapy
  • climate change
  • mass spectrometry