title: Characterization of the Kynurenine Pathway in CD8+Human Primary Monocyte-Derived Dendritic Cells.
abstract: The kynurenine (KYN) pathway (KP) is a major degradative pathway of the amino acid, L-tryptophan (TRP), that ultimately leads to the anabolism of the essential pyridine nucleotide, nicotinamide adenine dinucleotide. TRP catabolism results in the production of several important metabolites, including the major immune tolerance-inducing metabolite KYN, and the neurotoxin and excitotoxin quinolinic acid. Dendritic cells (DCs) have been shown to mediate immunoregulatory roles that mediated by TRP catabolism. However, characterization of the KP in human DCs has so far only been partly delineated. It is critical to understand which KP enzymes are expressed and which KP metabolites are produced to be able to understand their regulatory effects on the immune response. In this study, we characterized the KP in human monocyte-derived DCs (MDDCs) in comparison with the human primary macrophages using RT-PCR, high-pressure gas chromatography, mass spectrometry, and immunocytochemistry. Our results show that the KP is entirely expressed in human MDDC. Following activation of the KP using interferon gamma, MDDCs can mediate apoptosis of Thcells in vitro. Understanding the molecular mechanisms regulating KP metabolism in MDDCs may provide renewed insight for the development of novel therapeutics aimed at modulating immunological effects and peripheral tolerance.
authors: Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia. n.braidy@unsw.edu.au.
authors: Nady
authors: N
authors: Braidy
authors: St Vincent's Centre for Applied Medical Research, Sydney, Australia.
authors: Helene
authors: H
authors: Rossez
authors: Neuropharmacology Group, MND and Neurodegenerative Diseases Research Centre, Macquarie University, Sydney, NSW, 2109, Australia.
authors: Chai K
authors: CK
authors: Lim
authors: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors: Bat-Erdene
authors: BE
authors: Jugder
authors: St Vincent's Centre for Applied Medical Research, Sydney, Australia.|Department of Neurology and HIV Medicine, St Vincent's Hospital, Sydney, Australia.
authors: Bruce J
authors: BJ
authors: Brew
authors: Neuropharmacology Group, MND and Neurodegenerative Diseases Research Centre, Macquarie University, Sydney, NSW, 2109, Australia. gilles.guillemin@mq.edu.au.
authors: Gilles J
authors: GJ
authors: Guillemin
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D016827:CD8 Antigens / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007737:Kynurenine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D013058:Mass Spectrometry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; D007155:Immunologic Factors; D012333:RNA, Messenger; D007737:Kynurenine; D007371:Interferon-gamma
keywords: Human monocyte-derived dendritic cells; Indoleamine 2,3 dioxygenase; Kynurenine pathway; Quinolinic acid