The Kynurenine Pathway in Psoriasis: Mechanisms and Therapeutic Opportunities

Griffiths, C. E. M., A. W. Armstrong, J. E. Gudjonsson, and J. N. W. N. Barker. 2021. Psoriasis. Lancet 397 (10281): 1301–1315.

Article  CAS  PubMed  Google Scholar 

Armstrong, A. W., and C. Read. 2020. Pathophysiology, clinical presentation, and treatment of psoriasis a review. JAMA-Journal of the American Medical Association 323 (19): 1945–1960.

Article  CAS  Google Scholar 

National Psoriasis Foundation. Available from: https://www.psoriasis.org/content/statistics.

Huang, S., and Y. Bai. 2023. Knowledge mapping and research hotspots of comorbidities in psoriasis: A bibliometric analysis from 2004 to 2022. Medicina (Kaunas) 59 (2): 393.

Singh, S., C. Taylor, H. Kornmehl, and A. W. Armstrong. 2017. Psoriasis and suicidality: A systematic review and meta-analysis. Journal of the American Academy of Dermatology 77 (3): 425–440.

Article  PubMed  Google Scholar 

Mehrmal, S., P. Uppal, N. Nedley, R. L. Giesey, and G. R. Delost. 2021. The global, regional, and National burden of psoriasis in 195 countries and territories, 1990 to 2017: A systematic analysis from the global burden of disease study 2017. Journal of the American Academy of Dermatology 84 (1): 46–52.

Article  PubMed  Google Scholar 

Guo, J., H. Zhang, W. Lin, L. Lu, J. Su, and X. Chen. 2023. Signaling pathways and targeted therapies for psoriasis. Signal Transduction and Targeted Therapy 8 (1): 437.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ghoreschi, K., A. Balato, C. Enerback, and R. Sabat. 2021. Therapeutics targeting the Il-23 and Il-17 pathway in psoriasis. Lancet 397 (10275): 754–766.

Article  CAS  PubMed  Google Scholar 

Montoya-Londoño, D., C. A. Gómez-Mercado, J. I. Estrada-Acevedo, J. Madrigal-Cadavid, A. Segura, N. A. Giraldo-Alzate, and A. M. Londoño. 2022. Therapeutic failure in moderate and severe psoriasis patients in a health Institution - a transversal study of prevalence and demographic determinants. The Journal of Dermatological Treatment 33 (6): 2821–2826.

Article  PubMed  Google Scholar 

Wang, Xiao-Yu, Chun-Lei Zhang, and Wen-Hui Wang. 2020. Time to relapse after treatment withdrawal for different biologics used to treat plaque psoriasis. Chinese Medical Journal 133 (24): 2998–3000.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee, H. J., and M. Kim. 2023. Challenges and future trends in the treatment of psoriasis. International Journal of Molecular Sciences 24 (17):13313.

CAS  Google Scholar 

Al-Janabi, A., S. Eyre, A. C. Foulkes, A. R. Khan, N. Dand, E. Burova, B. DeSilva, A. Makrygeorgou, E. Davies, C. H. Smith, C. E. M. Griffiths, A. P. Morris, and R. B. Warren. 2023. Atopic polygenic risk score is associated with paradoxical eczema developing in patients with psoriasis treated with biologics. Journal of Investigative Dermatology 143 (8): 1470–1478.

Article  CAS  Google Scholar 

Xue, C., G. Li, Q. Zheng, X. Gu, Q. Shi, Y. Su, Q. Chu, X. Yuan, Z. Bao, J. Lu, and L. Li. 2023. Tryptophan metabolism in health and disease. Cell Metabolism 35 (8): 1304–1326.

Article  CAS  PubMed  Google Scholar 

Wang, Y., Y. Zhang, W. Wang, Y. Zhang, X. Dong, and Y. Liu. 2025. Diverse physiological roles of kynurenine pathway metabolites: updated implications for health and disease. Metabolites 15 (3): 210.

Ito, M., K. Ogawa, K. Takeuchi, A. Nakada, M. Heishi, H. Suto, K. Mitsuishi, Y. Sugita, H. Ogawa, and C. Ra. 2004. Gene expression of enzymes for Tryptophan degradation pathway is upregulated in the skin lesions of patients with atopic dermatitis or psoriasis. Journal of Dermatological Science 36 (3): 157–164.

Article  CAS  PubMed  Google Scholar 

Stone, T. W., and R. O. Williams. 2023. Modulation of T cells by Tryptophan metabolites in the kynurenine pathway. Trends in Pharmacological Sciences 44 (7): 442–456.

Article  CAS  PubMed  Google Scholar 

Szelest, M., K. Walczak, and T. Plech. 2021. A new insight into the potential role of Tryptophan-Derived Ahr ligands in skin physiological and pathological processes. International Journal of Molecular Sciences 22 (3): 1104.

Messaoud, A., R. Mensi, W. Douki, F. Neffati, M. F. Najjar, G. Gobbi, F. Valtorta, L. Gaha, and S. Comai. 2019. Reduced peripheral availability of Tryptophan and increased activation of the kynurenine pathway and cortisol correlate with major depression and suicide. The World Journal of Biological Psychiatry: the official Journal of the World Federation of Societies of Biological Psychiatry 20 (9): 703–711.

Article  PubMed  Google Scholar 

Zhao, L., Y. Suolang, D. Zhou, Y. Tang, and Y. Zhang. 2018. Bifidobacteria alleviate experimentally induced colitis by upregulating indoleamine 2, 3-Dioxygenase expression. Microbiology and Immunology 62 (2): 71–79.

Article  CAS  PubMed  Google Scholar 

Sulo, G., S. E. Vollset, O. Nygård, Ø. Midttun, P. M. Ueland, S. J. Eussen, E. R. Pedersen, and G. S. Tell. 2013. Neopterin and Kynurenine-Tryptophan ratio as predictors of coronary events in older adults, the Hordaland health study. International Journal of Cardiology 168 (2): 1435–1440.

Article  PubMed  Google Scholar 

Pedersen, E. R., N. Tuseth, S. J. Eussen, P. M. Ueland, E. Strand, G. F. Svingen, Ø. Midttun, K. Meyer, G. Mellgren, A. Ulvik, J. E. Nordrehaug, D. W. Nilsen, and O. Nygård. 2015. Associations of plasma kynurenines with risk of acute myocardial infarction in patients with stable angina pectoris. Arteriosclerosis, Thrombosis, and Vascular Biology 35 (2): 455–462.

Article  CAS  PubMed  Google Scholar 

Stepaniuk, A., A. Baran, and I. Flisiak. 2023. Kynurenine pathway in Psoriasis-a promising link? Dermatologic Therapy (Heidelberg) 13 (8): 1617–1627.

Article  CAS  Google Scholar 

Cervenka, I., L.Z. Agudelo, and J.L. Ruas. 2017. Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health. Science 357 (6349): 9794.

Mor, A., A. Tankiewicz-Kwedlo, M. Ciwun, J. Lewkowicz, and D. Pawlak. 2024. Kynurenines as a novel target for the treatment of inflammatory disorders. Cells 13 (15): 1259.

Wirthgen, E., A. Hoeflich, A. Rebl, and J. Günther. 2017. Kynurenic acid: The Janus-Faced role of an immunomodulatory tryptophan metabolite and its link to pathological conditions. Frontiers in Immunology 8:1957.

Article  PubMed  Google Scholar 

Van de Velde, L. A., X. J. Guo, L. Barbaric, A. M. Smith, T. H. Oguin 3rd, P. G. Thomas, and P. J. Murray. 2016. Stress kinase Gcn2 controls the proliferative fitness and trafficking of cytotoxic T cells independent of environmental amino acid sensing. Cell Reports 17 (9): 2247–2258.

Article  PubMed  Google Scholar 

Fiore, A., and P. J. Murray. 2021. Tryptophan and Indole metabolism in immune regulation. Current Opinion in Immunology 70:7–14.

Article  CAS  PubMed  Google Scholar 

Liu, Y., X. Liang, W. Dong, Y. Fang, J. Lv, T. Zhang, R. Fiskesund, J. Xie, J. Liu, X. Yin, X. Jin, D. Chen, K. Tang, J. Ma, H. Zhang, J. Yu, J. Yan, H. Liang, S. Mo, F. Cheng, Y. Zhou, H. Zhang, J. Wang, J. Li, Y. Chen, B. Cui, Z.W. Hu, X. Cao, F. Xiao-Feng, Qin, and B. Huang. 2018. Tumor-repopulating cells induce Pd-1 expression in Cd8(+) T cells by transferring kynurenine and Ahr activation. Cancer Cell 33 (3): 480–497.

Verdin, E. 2015. Nad⁺ in aging, metabolism, and neurodegeneration. Science 350 (6265): 1208–1213.

Article  CAS  PubMed  Google Scholar 

Llamas-Velasco, M., P. Bonay, M. J. Concha-Garzón, L. Corvo-Villén, A. Vara, D. Cibrián, A. Sanguino-Pascual, F. Sánchez-Madrid, H. de la Fuente, and E. Daudén. 2017. Immune cells from patients with psoriasis are defective in inducing indoleamine 2,3-Dioxygenase expression in response to inflammatory stimuli. British Journal of Dermatology 176 (3): 695–704.

Article  CAS  PubMed  Google Scholar 

Solvay, M., P. Holfelder, S. Klaessens, L. Pilotte, V. Stroobant, J. Lamy, S. Naulaerts, Q. Spillier, R. Frédérick, E. De Plaen, C. Sers, C. A. Opitz, B. J. Van den Eynde, and J. Zhu. 2023. Tryptophan depletion sensitizes the Ahr pathway by increasing Ahr expression and Gcn2/Lat1-Mediated kynurenine uptake, and potentiates induction of regulatory T lymphocytes. Journal for Immunotherapy of Cancer 11 (6): e006728.

Article  Google Scholar 

Carrillo-Mora, P., C. Landa-Solís, D. Valle-Garcia, A. Luna-Angulo, H. Avilés-Arnaut, B. Robles-Bañuelos, L. Sánchez-Chapul, and E. Rangel-López. 2024. Kynurenines and inflammation: A remarkable Axis for multiple sclerosis treatment. Pharmaceuticals (Basel) 17 (8): 983.

Campesato, L. F., S. Budhu, J. Tchaicha, C. H. Weng, M. Gigoux, I. J. Cohen, D. Redmond, L. Mangarin, S. Pourpe, C. Liu, R. Zappasodi, D. Zamarin, J. Cavanaugh, A. C. Castro, M. G. Manfredi, K. McGovern, T. Merghoub, and J. D. Wolchok. 2020. Blockade of the Ahr restricts a treg-macrophage suppressive axis induced by L-Kynurenine. Nature Communications 11 (1): 4011.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yu, N., C. Peng, W. J. Chen, Z. W. Sun, J. F. Zheng, S. J. Zhang, Y. F. Ding, and Y. L. Shi. 2021. Circulating metabolomic signature in generalized pustular psoriasis blunts monocyte hyperinflammation by triggering amino acid response. Frontiers in Immunology 12:739514.

Guo, L., C. Wu, B. Song, and H. Z. Jin. 2024. Exploration of circulating metabolic signature of erythrodermic psoriasis based on Lc-Ms metabolomics. Experimental Dermatology 33 (5): e15103.

Li, S. S., Y. Liu, H. Li, L. P. Wang, L. F. Xue, G. S. Yin, and X. S. Wu. 2019. Identification of psoriasis vulgaris biomarkers in human plasma by Non-Targeted metabolomics based on Uplc-Q-Tof/Ms. European Review for Medical and Pharmacological Sciences 23 (9): 3940–3950.

PubMed  Google Scholar 

Stepaniuk, A., A. Baran, J.M. Hermanowicz, B. Sieklucka, D. Pawlak, and I. Flisiak. 2025. Peripheral Kynurenine pathway metabolites in patients with psoriasis. International Journal of Molecular Sciences 26(7).

Elizei, S. S., M. Pakyari, M. Ghoreishi, R. Kilani, S. Mahmoudi, and A. Ghahary. 2018. Ido-expressing fibroblasts suppress the development of imiquimod-induced psoriasis-like dermatitis. Cell Transplantation 27 (3): 557–570.

Article  PubMed  PubMed Central  Google Scholar 

Bracho-Sanchez, E., F. G. Rocha, S. K. Bedingfield, B. D. Partain, S. L. Macias, M. A. Brusko, J. M. Colazo, M. M. Fettis, S. A. Farhadi, E. Y. Helm, K. Koenders, A. J. Kwiatkowski, A. Restuccia, B. S. Morales, A. Wanchoo, D. Avram, K. D. Allen, C. L. Duvall, S. M. Wallet, G. A. Hudalla, and B. G. Keselowsky. 2023. Suppression of local inflammation via galectin-anchored indoleamine 2,3-Dioxygenase. Nature Biomedical Engineering 7 (9): 1156–1169.

Article  CAS  PubMed  PubMed Central 

Comments (0)

No login
gif