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Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity
Ist Teil von
Science (American Association for the Advancement of Science), 2021-01, Vol.371 (6527), p.405-410
Ort / Verlag
United States: The American Association for the Advancement of Science
Erscheinungsjahr
2021
Link zum Volltext
Quelle
American Association for the Advancement of Science
Beschreibungen/Notizen
Infection triggers expansion and effector differentiation of T cells specific for microbial antigens in association with metabolic reprograming. We found that the glycolytic enzyme lactate dehydrogenase A (LDHA) is induced in CD8
T effector cells through phosphoinositide 3-kinase (PI3K) signaling. In turn, ablation of LDHA inhibits PI3K-dependent phosphorylation of Akt and its transcription factor target Foxo1, causing defective antimicrobial immunity. LDHA deficiency cripples cellular redox control and diminishes adenosine triphosphate (ATP) production in effector T cells, resulting in attenuated PI3K signaling. Thus, nutrient metabolism and growth factor signaling are highly integrated processes, with glycolytic ATP serving as a rheostat to gauge PI3K-Akt-Foxo1 signaling in the control of T cell immunity. Such a bioenergetic mechanism for the regulation of signaling may explain the Warburg effect.