| Autor: |
William J. Quinn, III, Jing Jiao, Tara TeSlaa, Jason Stadanlick, Zhonglin Wang, Liqing Wang, Tatiana Akimova, Alessia Angelin, Patrick M. Schäfer, Michelle D. Cully, Caroline Perry, Piotr K. Kopinski, Lili Guo, Ian A. Blair, Louis R. Ghanem, Michael S. Leibowitz, Wayne W. Hancock, Edmund K. Moon, Matthew H. Levine, Evgeniy B. Eruslanov, Douglas C. Wallace, Joseph A. Baur, Ulf H. Beier |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 33, Iss 11, Pp 108500- (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2020.108500 |
| Popis: |
Summary: Immune cell function is influenced by metabolic conditions. Low-glucose, high-lactate environments, such as the placenta, gastrointestinal tract, and the tumor microenvironment, are immunosuppressive, especially for glycolysis-dependent effector T cells. We report that nicotinamide adenine dinucleotide (NAD+), which is reduced to NADH by lactate dehydrogenase in lactate-rich conditions, is a key point of metabolic control in T cells. Reduced NADH is not available for NAD+-dependent enzymatic reactions involving glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and 3-phosphoglycerate dehydrogenase (PGDH). We show that increased lactate leads to a block at GAPDH and PGDH, leading to the depletion of post-GAPDH glycolytic intermediates, as well as the 3-phosphoglycerate derivative serine that is known to be important for T cell proliferation. Supplementing serine rescues the ability of T cells to proliferate in the presence of lactate-induced reductive stress. Directly targeting the redox state may be a useful approach for developing novel immunotherapies in cancer and therapeutic immunosuppression. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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