The Kynurenine Pathway in Psoriasis: Mechanisms and Therapeutic Opportunities

银屑病中的犬尿氨酸通路:机制和治疗机遇

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Abstract

Psoriasis is a chronic inflammatory disease driven by genetic and environmental factors, with pathogenesis closely linked to metabolic reprogramming and immune microenvironment dysregulation. The kynurenine pathway (KP), as the principal route of tryptophan catabolism, plays a pivotal role in regulating immune tolerance, oxidative stress, and neuroinflammation, thereby serving as a "metabolic bridge" that links cutaneous lesions to systemic comorbidities in psoriasis. This review systematically examines the pathological mechanisms of KP in psoriasis. Imbalances in the activities of indoleamine 2,3-dioxygenase (IDO) and kynureninase (KYNU) in patients with psoriasis lead to a pro-inflammatory shift in KP. Moreover, downstream KP metabolites mediate oxidative damage, endothelial dysfunction, and depletion of serotonin, which are closely associated with the increased risk of cardiovascular disease and depressive disorders commonly observed in psoriasis. Although therapeutic strategies targeting the KP, such as IDO overexpression and KYNU inhibition, have demonstrated promising potential, the complexity of the metabolic network and tissue-specific effects limit the clinical application of single-target therapies. Future studies should integrate multi-omics data to elucidate the dynamic regulatory network of the KP, develop multi-targeted modulators, and explore new paradigms for coordinated management of cutaneous and systemic comorbidities, thereby providing a solid theoretical foundation for precision treatment of psoriasis.

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