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01-11-2016 | Original Article

Characterization of the Kynurenine Pathway in CD8⁺ Human Primary Monocyte-Derived Dendritic Cells

Authors: Nady Braidy, Helene Rossez, Chai K. Lim, Bat-Erdene Jugder, Bruce J. Brew, Gilles J. Guillemin

Published in: Neurotoxicity Research | Issue 4/2016

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 T _h cells 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.

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Title: Characterization of the Kynurenine Pathway in CD8+ Human Primary Monocyte-Derived Dendritic Cells
Authors: Nady Braidy
Helene Rossez
Chai K. Lim
Bat-Erdene Jugder
Bruce J. Brew
Gilles J. Guillemin
Publication date: 01-11-2016
Publisher: Springer US
Published in: Neurotoxicity Research / Issue 4/2016
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-016-9657-x

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Characterization of the Kynurenine Pathway in CD8⁺ Human Primary Monocyte-Derived Dendritic Cells

Abstract

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Abstract

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