Lactate fluxes in T cell function

Abstract : Cellular metabolism is critical for T cell function and differentiation. Quiescent T cells rely exclusively on oxidative phosphorylation for energy production. However, once activated, proliferating T cells must undergo metabolic reprogramming which promotes glucose uptake and glycolytic flux accompanied by a metabolic switch toward production of lipids, proteins, nucleic acids and other carbohydrates. Moreover, recent evidence supports the notion that a switch towards aerobic glycolysis is specifically required for proper effector function in T cells. Increased glycolytic flux in cells causes lactic acid accumulation with a consequent drop in intracellular pH. This, in turn, slow down glycolysis. Therefore, limiting excessive concentration of lactic acid in the cytoplasm is required in cell types relying on glycolysis for proliferation and function. Lactic acid efflux from cells is carried out by some members of the Slc16 gene family, the monocarboxylate transporters MCT1-4. These transporters catalyse the proton-linked transport of monocarboxylates such as L-lactate, pyruvate and ketone bodies across the plasma membrane, of which L-lactate is quantitatively by far the most important substrate. How lactate fluxes are carried out in T cells has not been directly established. The project takes advantage of mice whose T cells are genetically invalidated for MCTs expression to identify the exact role played by lactate fluxes in T cell function.
Promoteur/Supervisor : Prof. BRAUN Michel
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Centre de recherche/Research center : Institute for Medical Immunology (IMI)
Faculté/Faculty : Faculty of Medicine/Faculté de Médecine
Ecole doctorale/Graduate Colleges : Biomedical and Pharmaceutical Science/Sciences biomédicales et pharmaceutiques
Ecole doctorale thématique/Graduate School (French Only): Cancérologie expérimentale

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