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Review

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

1
MTA-SZTE—Neuroscience Research Group, H-6725 Szeged, Hungary
2
Interdisciplinary Excellence Centre, Department of Neurology, Faculty of Medicine, University of Szeged, H-6725 Szeged, Hungary
3
Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary
*
Author to whom correspondence should be addressed.
Academic Editor: Rosanna Di Paola
Biomedicines 2021, 9(7), 734; https://doi.org/10.3390/biomedicines9070734
Received: 10 June 2021 / Revised: 21 June 2021 / Accepted: 23 June 2021 / Published: 25 June 2021
The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases and psychiatric disorders. The presence of positive feedback loops facilitates amplifying the immune responses vice versa. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses and chronic diseases. KYN, kynurenic acid, xanthurenic acid and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2,3-dioxygenases and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric disorders, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia and autism spectrum disorder. View Full-Text
Keywords: chronic inflammation; low-grade inflammation; immune tolerance; inflammatory factor; kynurenine; kynurenic acid; depression; bipolar disorder; substance use disorder; post-traumatic stress disorder; schizophrenia; autism spectrum disorder chronic inflammation; low-grade inflammation; immune tolerance; inflammatory factor; kynurenine; kynurenic acid; depression; bipolar disorder; substance use disorder; post-traumatic stress disorder; schizophrenia; autism spectrum disorder
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MDPI and ACS Style

Tanaka, M.; Tóth, F.; Polyák, H.; Szabó, Á.; Mándi, Y.; Vécsei, L. Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway. Biomedicines 2021, 9, 734. https://doi.org/10.3390/biomedicines9070734

AMA Style

Tanaka M, Tóth F, Polyák H, Szabó Á, Mándi Y, Vécsei L. Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway. Biomedicines. 2021; 9(7):734. https://doi.org/10.3390/biomedicines9070734

Chicago/Turabian Style

Tanaka, Masaru, Fanni Tóth, Helga Polyák, Ágnes Szabó, Yvette Mándi, and László Vécsei. 2021. "Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway" Biomedicines 9, no. 7: 734. https://doi.org/10.3390/biomedicines9070734

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