Inhibition of indoleamine 2,3-dioxygenase in mixed lymphocyte reaction affects glucose influx and enzymes involved in aerobic glycolysis and glutaminolysis in alloreactive T-cells
| Autor: | Efi Yiannaki, Georgia Antoniadi, Dimitra Markala, Spyridon Arampatzis, Vassilios Liakopoulos, Ioannis Stefanidis, Theodoros Eleftheriadis, Georgios Pissas |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Citric Acid Cycle Immunology mTORC1 Mechanistic Target of Rapamycin Complex 1 Protein Serine-Threonine Kinases Biology Enzyme activator T-Lymphocyte Subsets Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Immunology and Allergy Glycolysis Glucose Transporter Type 1 Glutaminolysis TOR Serine-Threonine Kinases Tryptophan General Medicine Enzyme Activation Citric acid cycle Metabolic pathway Glucose Biochemistry Anaerobic glycolysis Multiprotein Complexes Leukocytes Mononuclear Lymphocyte Culture Test Mixed |
| Zdroj: | Human Immunology. 74:1501-1509 |
| ISSN: | 0198-8859 |
| DOI: | 10.1016/j.humimm.2013.08.268 |
| Popis: | Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity. T-cell proliferation and differentiation to effector cells require increased glucose consumption, aerobic glycolysis and glutaminolysis. The effect of IDO on the above metabolic pathways was evaluated in alloreactive T-cells. Mixed lymphocyte reaction (MLR) in the presence or not of the IDO inhibitor, 1-methyl-dl-tryptophan (1-MT), was used. In MLRs, 1-MT decreased tryptophan consumption, increased cell proliferation, glucose influx and lactate production, whereas it decreased tricarboxylic acid cycle activity. In T-cells, from the two pathways that could sense tryptophan depletion, i.e. general control nonrepressed 2 (GCN2) kinase and mammalian target of rapamycin complex 1, 1-MT reduced only the activity of the GCN2 kinase. Additionally 1-MT treatment of MLRs altered the expression and/or the phosphorylation state of glucose transporter-1 and of key enzymes involved in glucose metabolism and glutaminolysis in alloreactive T-cells in a way that favors glucose influx, aerobic glycolysis and glutaminolysis. Thus in alloreactive T-cells, IDO through activation of the GCN2 kinase, decreases glucose influx and alters key enzymes involved in metabolism, decreasing aerobic glycolysis and glutaminolysis. Acting in such a way, IDO could be considered as a constraining factor for alloreactive T-cell proliferation and differentiation to effector T-cell subtypes. |
| Databáze: | OpenAIRE |
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