title: The indoleamine 2,3-dioxygenase inhibitor 1-methyl-tryptophan suppresses mitochondrial function, induces aerobic glycolysis and decreases interleukin-10 production in human lymphocytes.
abstract: BACKGROUND
  Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity. It is known that IDO induces T-cell differentiation to regulatory T-cells (Treg) through tryptophan depletion and/or kynurenine pathway products. CD4+ effector T-cells require distinct metabolic programs in order to support their function as compared to Treg cells. Furthermore, glucose metabolism is also known to affect B-cell survival and function. The effect of IDO on glucose metabolism of lymphocytes was evaluated by using its inhibitor 1-methyl-DL-tryptophan (1-MT).
  
  
  METHODS
  Ten healthy volunteers vaccinated against tetanus. Peripheral blood mononuclear cells (PBMC) were cultured with or without tetanus toxoid and/or 1-MT. Cell proliferation was assessed by optical microscopy, glucose uptake by measuring its concentration in the supernatant, aerobic glycolysis by assessing lactate concentration in the supernatant, mitochondrial function by XTT assay, and finally production of Tregs' signature cytokine IL-10 by means of ELISA.
  
  
  RESULTS
  Primarily, IDO decreases glucose uptake by stimulated lymphocytes. Secondly, IDO increases mitochondrial function in stimulated lymphocytes. In addition, IDO decreases aerobic glycolysis in stimulated lymphocytes. Finally, IDO induces the production of the immunosuppressive cytokine IL-10 by stimulated lymphocytes.
  
  
  CONCLUSIONS
  Considering that cell metabolism plays a significant role in lymphocyte differentiation and function, IDO may exert its immunomodulatory effect by interfering with cell metabolism.
authors.affiliation: Department of Nephrology.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Eleftheriadis
authors.forename: Georgios
authors.initials: G
authors.lastname: Pissas
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Karioti
authors.forename: Georgia
authors.initials: G
authors.lastname: Antoniadi
authors.forename: Vassilios
authors.initials: V
authors.lastname: Liakopoulos
authors.forename: Konstantina
authors.initials: K
authors.lastname: Dafopoulou
authors.forename: Spyros
authors.initials: S
authors.lastname: Pournaras
authors.forename: Georgios
authors.initials: G
authors.lastname: Koukoulis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Stefanidis
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D016753:Interleukin-10 / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D013745:Tetanus Toxoid / Q000494:pharmacology; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D013745:Tetanus Toxoid; D016753:Interleukin-10; D014364:Tryptophan; D005947:Glucose