Involvement of the tryptophan-kynurenine pathway in the pathogenesis of autoimmune diseases
The kynurenine pathway (KP), a major metabolic pathway for L-tryptophan (Trp) in mammals, plays a multifaceted role in various physiological processes, including neural activity, immune system regulation, and the maintenance of intestinal homeostasis. The functional connection between the KP and imm...
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| Language: | English |
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Elsevier
2025-10-01
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| Series: | Experimental Gerontology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556525001664 |
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| author | A-Yuan Chen Ying-Jie Zhao Yue-Ye Wang Wei Wei Wei Hu Yan Chang |
| author_facet | A-Yuan Chen Ying-Jie Zhao Yue-Ye Wang Wei Wei Wei Hu Yan Chang |
| author_sort | A-Yuan Chen |
| collection | DOAJ |
| description | The kynurenine pathway (KP), a major metabolic pathway for L-tryptophan (Trp) in mammals, plays a multifaceted role in various physiological processes, including neural activity, immune system regulation, and the maintenance of intestinal homeostasis. The functional connection between the KP and immune system is supported by robust evidence, including disease-associated alterations in KP metabolite concentrations and enzyme activities that correlate with immune function changes. Imbalances in the KP can be detrimental, as excessive production of pro- or anti-inflammatory metabolites may promote autoimmunity or impair pathogen defense. To date, KP enzymes and metabolites have been extensively studied as both promoters and therapeutic targets in a wide array of autoimmune diseases (AID). Pharmacological modulation of the KP represents a promising therapeutic strategy, as it can regulate immune responses and attenuate disease progression in AID. However, the precise cellular and molecular mechanisms by which the KP contributes to AID pathogenesis remain incompletely understood. This review explores the complex mechanisms through which KP enzymes and metabolites regulate inflammatory immune responses in AID, and highlights potential therapeutic targets for drug development. |
| format | Article |
| id | doaj-art-b9186c57b2a9499db3c31eefefbc90f4 |
| institution | DOAJ |
| issn | 1873-6815 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental Gerontology |
| spelling | doaj-art-b9186c57b2a9499db3c31eefefbc90f42025-08-20T03:13:59ZengElsevierExperimental Gerontology1873-68152025-10-0120911283710.1016/j.exger.2025.112837Involvement of the tryptophan-kynurenine pathway in the pathogenesis of autoimmune diseasesA-Yuan Chen0Ying-Jie Zhao1Yue-Ye Wang2Wei Wei3Wei Hu4Yan Chang5Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, ChinaThe Second Affiliated Hospital of Anhui Medical University, Hefei 230032, ChinaInstitute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, ChinaInstitute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China; Corresponding authors.The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Corresponding authors.Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China; Laboratory Animal Center, Anhui Medical University, Hefei 230032, China; Correspondence to: Y. Chang, Laboratory Animal Center, Anhui Medical University, Hefei 230032, China.The kynurenine pathway (KP), a major metabolic pathway for L-tryptophan (Trp) in mammals, plays a multifaceted role in various physiological processes, including neural activity, immune system regulation, and the maintenance of intestinal homeostasis. The functional connection between the KP and immune system is supported by robust evidence, including disease-associated alterations in KP metabolite concentrations and enzyme activities that correlate with immune function changes. Imbalances in the KP can be detrimental, as excessive production of pro- or anti-inflammatory metabolites may promote autoimmunity or impair pathogen defense. To date, KP enzymes and metabolites have been extensively studied as both promoters and therapeutic targets in a wide array of autoimmune diseases (AID). Pharmacological modulation of the KP represents a promising therapeutic strategy, as it can regulate immune responses and attenuate disease progression in AID. However, the precise cellular and molecular mechanisms by which the KP contributes to AID pathogenesis remain incompletely understood. This review explores the complex mechanisms through which KP enzymes and metabolites regulate inflammatory immune responses in AID, and highlights potential therapeutic targets for drug development.http://www.sciencedirect.com/science/article/pii/S0531556525001664Autoimmune diseaseTryptophanKynurenine pathwayIndoleamine 2,3-dioxygenaseTryptophan 2,3- dioxygenaseMetabolism |
| spellingShingle | A-Yuan Chen Ying-Jie Zhao Yue-Ye Wang Wei Wei Wei Hu Yan Chang Involvement of the tryptophan-kynurenine pathway in the pathogenesis of autoimmune diseases Experimental Gerontology Autoimmune disease Tryptophan Kynurenine pathway Indoleamine 2,3-dioxygenase Tryptophan 2,3- dioxygenase Metabolism |
| title | Involvement of the tryptophan-kynurenine pathway in the pathogenesis of autoimmune diseases |
| title_full | Involvement of the tryptophan-kynurenine pathway in the pathogenesis of autoimmune diseases |
| title_fullStr | Involvement of the tryptophan-kynurenine pathway in the pathogenesis of autoimmune diseases |
| title_full_unstemmed | Involvement of the tryptophan-kynurenine pathway in the pathogenesis of autoimmune diseases |
| title_short | Involvement of the tryptophan-kynurenine pathway in the pathogenesis of autoimmune diseases |
| title_sort | involvement of the tryptophan kynurenine pathway in the pathogenesis of autoimmune diseases |
| topic | Autoimmune disease Tryptophan Kynurenine pathway Indoleamine 2,3-dioxygenase Tryptophan 2,3- dioxygenase Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S0531556525001664 |
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