Table Info

Table 1.

Differences in the serum concentrations of TRP-KYN pathway metabolites between HCs and PSOs

Metabolites	HCs (mean ± SD)	PSOs (mean ± SD)
TRP (μM)	52.9 ± 7.26	48.0 ± 8.34	**
KYN (μM)	2.00 ± 0.49	1.73 ± 0.47	**
KYNA (nM)	37.6 ± 9.81	32.0 ± 16.8	*
AA (nM)	17.1 ± 6.78	16.0 ± 12.2
3HK (nM)	18.8 ± 12.9	18.6 ± 8.76
3HAA (nM)	7.56 ± 4.52	14.2 ± 6.22	***

P < 0.05; ^**P < 0.01;^***P < 0.001 vs. HCs

Declarations

Acknowledgments

The authors would like to thank Mrs. Kayoko Tanaka for assisting data collection.

Author contributions

Seishima M and KS contributed conception and design of the study; RS and YY performed the experiments; KF and YM organized the database; Sakurai M and YY performed the statistical analysis; Seishima M wrote the first draft of the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Ethical approval

The study protocol was approved by the ethics committee of Gifu University Graduate School of Medicine (2018–1949).

Consent to participate

The informed consent to participate in the study was obtained from all participants.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Szelest M, Walczak K, Plech T. A new insight into the potential role of tryptophan-derived AhR ligands in skin physiological and pathological processes. Int J Mol Sci. 2021;22:1104. [DOI] [PubMed] [PMC]

Kamata M, Tada Y. Safety of biologics in psoriasis. J Dermatol. 2018;45:279–86. [DOI] [PubMed]

Visser MJE, Venter C, Roberts TJ, Tarr G, Pretorius E. Psoriatic disease is associated with systemic inflammation, endothelial activation, and altered haemostatic function. Sci Rep. 2021;11:13043. [DOI] [PubMed] [PMC]

Dowlatshahi EA, van der Voort EA, Arends LR, Nijsten T. Markers of systemic inflammation in psoriasis: a systematic review and meta-analysis. Br J Dermatol. 2013;169:266–82. [DOI] [PubMed]

Harden JL, Lewis SM, Lish SR, Suárez-Fariñas M, Gareau D, Lentini T, et al. The tryptophan metabolism enzyme L-kynureninase is a novel inflammatory factor in psoriasis and other inflammatory diseases. J Allergy Clin Immunol. 2016;137:1830–40. [DOI] [PubMed] [PMC]

Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 1998;281:1191–3. [DOI] [PubMed]

Fallarino F, Grohmann U, You S, McGrath BC, Cavener DR, Vacca C, et al. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol. 2006;176:6752–61. [DOI] [PubMed]

Gostner JM, Becker K, Kofler H, Strasser B, Fuchs D. Tryptophan metabolism in allergic disorders. Int Arch Allergy Immunol. 2016;169:203–15. [DOI] [PubMed] [PMC]

Harden JL, Gu T, Kilinc MO, Rowswell-Turner RB, Virtuoso LP, Egilmezet NK, et al. Dichotomous effects of IFN-gamma on dendritic cell function determine the extent of IL-12-driven antitumor T cell immunity. J Immunol. 2011;187:126–32. [DOI] [PubMed] [PMC]

10.

Gu T, Rowswell-Turner RB, Kilinc MO, Egilmez NK. Central roleof IFNgamma-indoleamine 2,3-dioxygenase axis in regulation of interleukin-12-mediated antitumor immunity. Cancer Res. 2010;70:129–38. [DOI] [PubMed] [PMC]

11.

Ito M, Ogawa K, Takeuchi K, Nakada A, Heishi M, Suto H, et al. Gene expression of enzymes for tryptophan degradation pathway is upregulated in the skin lesions of patients with atopic dermatitis or psoriasis. J Dermatol Sci. 2004;36:157–64. [DOI] [PubMed]

12.

Pantouris G, Serys M, Yuasa HJ, Ball HJ, Mowat CG. Human indoleamine 2,3-dioxygenase-2 has substrate specificity and inhibition characteristics distinct from those of indoleamine 2,3-dioxygenase-1. Amino Acids. 2014;46:2155–63. [DOI] [PubMed]

13.

Lowes MA, Suarez-Farinas M, Krueger JG. Immunology of psoriasis. Annu Rev Immunol. 2014;32:227–55. [DOI] [PubMed] [PMC]

14.

Tian S, Krueger JG, Li K, Jabbari A, Brodmerkel C, Lowes MA, et al. Meta-analysis derived (MAD) transcriptome of psoriasis defines the “core” pathogenesis of disease. PLoS One. 2012;7:e44274. [DOI] [PubMed] [PMC]

15.

Gudjonsson JE, Ding J, Johnston A, Tejasvi T, Guzman AM, Nair RP, et al. Assessment of the psoriatic transcriptome in a large sample: additional regulated genes and comparisons with in vitro models. J Invest Dermatol. 2010;130:1829–40. [DOI] [PubMed] [PMC]

16.

Mitsui H, Suárez-Fariñas M, Belkin DA, Levenkova N, Fuentes-Duculan J, Coats I, et al. Combined use of laser capture microdissection and cDNA microarray analysis identifies locally expressed disease-related genes in focal regions of psoriasis vulgaris skin lesions. J Invest Dermatol. 2012;132:1615–26. [DOI] [PubMed] [PMC]

17.

Suárez-Fariñas M, Fuentes-Duculan J, Lowes MA, Krueger JG. Resolved psoriasis lesions retain expression of a subset of disease-related genes. J Invest Dermatol. 2011;131:391–400. [DOI] [PubMed] [PMC]

18.

Chiricozzi A, Guttman-Yassky E, Suárez-Fariñas M, Nograles KE, Tian S, Cardinale I, et al. Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol. 2011;131:677–87. [DOI] [PubMed]

19.

Van der Leek AP, Yanishevsky Y, Kozyrskyj AL. The kynurenine pathway as a novel link between allergy and the gut microbiome. Front Immunol. 2017;8:1374. [DOI] [PubMed] [PMC]

20.

Sakurai M, Yamamoto Y, Kanayama N, Hasegawa M, Mouri A, Takemura M, et al. Serum metabolic profiles of the tryptophan-kynurenine pathway in the high risk subjects of major depressive disorder. Sci Rep. 2020;10:1961. [DOI] [PubMed] [PMC]

21.

Llamas-Velasco M, Bonay P, Concha-Garzón MJ, Corvo-Villén L, Vara A, Cibrián D, et al. Immune cells from patients with psoriasis are defective in inducing indoleamine 2,3-dioxygenase expression in response to inflammatory stimuli. Br J Dermatol. 2017;176:695–704. [DOI] [PubMed]

22.

Nomura I, Gao B, Boguniewicz M, Darst MA, Travers JB, Leung DY. Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. J Allergy Clin Immunol. 2003;112:1195–202. [DOI] [PubMed]

23.

Mellor AL, Baban B, Chandler P, Marshall B, Jhaver K, Hansen A, et al. Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J Immunol. 2003;171:1652–5. [DOI] [PubMed]

24.

DiNatale BC, Murray IA, Schroeder JC, Flaveny CA, Lahoti TS, Laurenzana EM, et al. Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicol Sci. 2010;115:89–97. [DOI] [PubMed] [PMC]

25.

Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol. 2010;185:3190–8. [DOI] [PubMed] [PMC]

26.

Julliard W, Fechner JH, Mezrich JD. The aryl hydrocarbon receptor meets immunology: friend or foe? A little of both. Front Immunol. 2014;5:458. [DOI] [PubMed] [PMC]

27.

Fujii K, Yamamoto Y, Mizutani Y, Saito K, Seishima M. Indoleamine 2,3-dioxygenase 2 deficiency exacerbates imiquimod-induced psoriasis-like skin inflammation. Int J Mol Sci. 2020;21:5515. [DOI]

28.

Darlington LG, Forrest CM, Mackay GM, Smith RA, Smith AJ, Nicholas Stoy N, et al. On the biological importance of the 3-hydroxyanthranilic acid: anthranilic acid ratio. Int J Tryptophan Res. 2010;3:51–9. [DOI] [PubMed] [PMC]

29.

Badawy AA. Hypothesis kynurenic and quinolinic acids: the main players of the kynurenine pathway and opponents in inflammatory disease. Med Hypotheses. 2018;118:129–38. [DOI] [PubMed]

30.

Takahashi H, Tsuji H, Hashimoto Y, Ishida-Yamamoto A, Iizuka H. Serum cytokines and growth factor levels in Japanese patients with psoriasis. Clin Exp Dermatol. 2010;35:645–9. [DOI] [PubMed]

31.

Solberg SM, Sandvik LF, Eidsheim M, Jonsson R, Bryceson YT, et al. Serum cytokine measurements and biological therapy of psoriasis-prospects for personalized treatment? Scand J Immunol. 2018;88:e12725. [DOI] [PubMed]

32.

Salimi Elizei S, Poormasjedi-Meibod MS, Wang X, Kheirandish M, Ghahary A. Kynurenic acid downregulates IL-17/1L-23 axis in vitro. Mol Cell Biochem. 2017;431:55–65. [DOI] [PubMed]

33.

Cochez PM, Michiels C, Hendrickx E, Van Belle AB, Lemaire MM, Dauguet N, et al. AhR modulates the IL-22-producing cell proliferation/recruitment in imiquimod-induced psoriasis mouse model. Eur J Immunol. 2016;46:1449–59. [DOI] [PubMed]

34.

di Meglio P, Duarte JH, Ahlfors H, Owens NDL, Li Y, Villanova F, et al. Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions. Immunity. 2014;40:989–1001. [DOI] [PubMed] [PMC]

35.

Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature. 2011;478:197–203. [DOI] [PubMed]

36.

Giustizieri ML, Mascia F, Frezzolini A, De Pità O, Chinni LM, Giannetti A, et al. Keratinocytes from patients with atopic dermatitis and psoriasis show a distinct chemokine production profile in response to T cell-derived cytokines. J Allergy Clin Immunol. 2001;107:871–7. [DOI] [PubMed]

37.

Kakinuma T, Saeki H, Tsunemi Y, Fujita H, Asano N, Mitsui H, et al. Increased serum cutaneous T cell-attracting chemokine (CCL27) levels in patients with atopic dermatitis and psoriasis vulgaris. J Allergy Clin Immunol. 2003;111:592–7. [DOI] [PubMed]

38.

Kwidzinski E, Bechmann I. IDO expression in the brain: a double-edged sword. J Mol Med (Berl). 2007;85:1351–9. [DOI] [PubMed]

39.

Vécsei L, Szalárdy L, Fülöp F, Toldi J. Kynurenines in the CNS: recent advances and new questions. Nat Rev Drug Discov. 2013;12:64–82. [DOI] [PubMed]