色氨酸和精氨酸代谢对免疫反应的调控机制及其在银屑病发病中的作用研究进展

doi:10.35541/cjd.20240377

Abstract

Abstract: 【Abstract】 Amino acid metabolism plays a key role in regulating immune responses and in the pathogenesis of autoimmune diseases. Psoriasis is a common chronic autoimmune skin disease, whose pathogenesis involves the imbalance of dendritic cells, T cells and other immune cells. Growing evidence indicates that the imbalance of certain amino acids and their metabolic process in psoriasis are related to the pathogenesis of psoriasis, with tryptophan and arginine metabolism being relatively well-studied. They play important roles in the pathogenesis of psoriasis by regulating immune response, and may also provide new therapeutic targets. This review summarizes the metabolic process of tryptophan and arginine as well as their regulatory effects on the immune system, and discusses the current research advances regarding their roles in the pathogenesis of psoriasis, aiming to provide a novel perspective on the pathogenesis of psoriasis, potentially facilitating new approaches for disease intervention.

Key words: Amino acid metabolism, Tryptophan, Arginine, Immune regulation, Psoriasis

Guo Lan, Jin Hongzhong. Tryptophan and arginine metabolism in immune regulation and their role in the pathogenesis of psoriasis[J]. Chinese Journal of Dermatology,2026,e20240377. doi:10.35541/cjd.20240377

References ［53］

［1］	Grohmann U, Mondanelli G, Belladonna ML, et al. Amino⁃acid sensing and degrading pathways in immune regulation［J］. Cytokine Growth Factor Rev, 2017,35:37⁃45. DOI: 10.1016/j.cytogfr.2017.05.004.
［2］	Grohmann U, Bronte V. Control of immune response by amino acid metabolism［J］. Immunol Rev, 2010,236:243⁃264. DOI: 10. 1111/j.1600⁃065X.2010.00915.x.
［3］	Mondanelli G, Iacono A, Carvalho A, et al. Amino acid metabolism as drug target in autoimmune diseases［J］. Autoimmun Rev, 2019,18（4）:334⁃348. DOI: 10.1016/j.autrev. 2019.02.004.
［4］	Correale J. Immunosuppressive amino⁃acid catabolizing enzymes in multiple sclerosis［J］. Front Immunol, 2020,11:600428. DOI: 10.3389/fimmu.2020.600428.
［5］	Murray PJ. Amino acid auxotrophy as a system of immunological control nodes［J］. Nat Immunol, 2016,17（2）:132⁃139. DOI: 10. 1038/ni.3323.
［6］	Merlo L, Grabler S, DuHadaway JB, et al. Therapeutic antibody targeting of indoleamine⁃2,3⁃dioxygenase （IDO2） inhibits autoimmune arthritis［J］. Clin Immunol, 2017,179:8⁃16. DOI: 10. 1016/j.clim.2017.01.016.
［7］	Shellard EM, Rane SS, Eyre S, et al. Functional genomics and insights into the pathogenesis and treatment of psoriasis［J］. Biomolecules, 2024,14（5）. DOI: 10.3390/biom14050548.
［8］	Xue C, Li G, Zheng Q, et al. Tryptophan metabolism in health and disease［J］. Cell Metab, 2023,35（8）:1304⁃1326. DOI: 10. 1016/j.cmet.2023.06.004.
［9］	Fiore A, Murray PJ. Tryptophan and indole metabolism in immune regulation［J］. Curr Opin Immunol, 2021,70:7⁃14. DOI: 10.1016/j.coi.2020.12.001.
［10］	Badawy AA. Kynurenine Pathway of tryptophan metabolism: regulatory and functional aspects［J］. Int J Tryptophan Res, 2017,10:1178646917691938. DOI: 10.1177/1178646917691938.
［11］	Basson C, Serem JC, Hlophe YN, et al. The tryptophan⁃kynurenine pathway in immunomodulation and cancer metastasis［J］. Cancer Med, 2023,12（18）:18691⁃18701. DOI: 10.1002/cam4.6484.
［12］	Agus A, Planchais J, Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease［J］. Cell Host Microbe, 2018,23（6）:716⁃724. DOI: 10.1016/j.chom.2018.05.003.
［13］	Eminel S, Jin N, Rostami M, et al. Dimethyl⁃ and monomethylfumarate regulate indoleamine 2,3⁃dioxygenase （IDO） activity in human immune cells［J］. Exp Dermatol, 2017,26（8）:685⁃690. DOI: 10.1111/exd.13138.
［14］	Harden JL, Lewis SM, Lish SR, et al. The tryptophan metabolism enzyme L⁃kynureninase is a novel inflammatory factor in psoriasis and other inflammatory diseases［J］. J Allergy Clin Immunol, 2016,137（6）:1830⁃1840. DOI: 10.1016/j.jaci.2015.09.055.
［15］	Cervenka I, Agudelo LZ, Ruas JL. Kynurenines: tryptophan's metabolites in exercise, inflammation, and mental health［J］. Science, 2017,357（6349）:aaf9794. DOI: 10.1126/science.aaf9794.
［16］	Fallarino F, Grohmann U, You S, 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］. J Immunol, 2006,176（11）:6752⁃6761. DOI: 10. 4049/jimmunol.176.11.6752.
［17］	Amobi A, Qian F, Lugade AA, et al. Tryptophan catabolism and cancer immunotherapy targeting IDO mediated immune suppression［J］. Adv Exp Med Biol, 2017,1036:129⁃144. DOI: 10.1007/978⁃3⁃319⁃67577⁃0_9.
［18］	Mezrich JD, Fechner JH, Zhang X, et al. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells［J］. J Immunol, 2010,185（6）:3190⁃3198. DOI: 10.4049/jimmunol.0903670.
［19］	Stone TW, Williams RO. Modulation of T cells by tryptophan metabolites in the kynurenine pathway［J］. Trends Pharmacol Sci, 2023,44（7）:442⁃456. DOI: 10.1016/j.tips.2023.04.006.
［20］	Guo L, Jin H. Research progress of metabolomics in psoriasis［J］. Chin Med J （Engl）, 2023,136（15）:1805⁃1816. DOI: 10. 1097/CM9.0000000000002504.
［21］	Li SS, Liu Y, Li H, et al. Identification of psoriasis vulgaris biomarkers in human plasma by non⁃targeted metabolomics based on UPLC⁃Q⁃TOF/MS［J］. Eur Rev Med Pharmacol Sci, 2019,23（9）:3940⁃3950. DOI: 10.26355/eurrev_201905_17823.
［22］	Chen C, Hou G, Zeng C, et al. Metabolomic profiling reveals amino acid and carnitine alterations as metabolic signatures in psoriasis［J］. Theranostics, 2021,11（2）:754⁃767. DOI: 10.7150/thno.51154.
［23］	Miao H, Bai Y, Shen S, et al. Biological agent exerts therapeutic effects by reversing abnormalities in amino acid metabolic pathways in psoriasis［J］. Exp Dermatol, 2024,33（3）:e15059. DOI: 10.1111/exd.15059.
［24］	Yu N, Peng C, Chen W, et al. Circulating metabolomic signature in generalized pustular psoriasis blunts monocyte hyperinflammation by triggering amino acid response［J］. Front Immunol, 2021,12:739514. DOI: 10.3389/fimmu.2021.739514.
［25］	Guo L, Wu C, Song B, et al. Exploration of circulating metabolic signature of erythrodermic psoriasis based on LC⁃MS metabolomics［J］. Exp Dermatol, 2024,33（5）:e15103. DOI: 10.1111/exd.15103.
［26］	Llamas⁃Velasco M, Bonay P, José Concha⁃Garzón M, et al. Immune cells from patients with psoriasis are defective in inducing indoleamine 2,3⁃dioxygenase expression in response to inflammatory stimuli［J］. Br J Dermatol, 2017,176（3）:695⁃704. DOI: 10.1111/bjd.14779.
［27］	Ito M, Ogawa K, Takeuchi K, et al. Gene expression of enzymes for tryptophan degradation pathway is upregulated in the skin lesions of patients with atopic dermatitis or psoriasis［J］. J Dermatol Sci, 2004,36（3）:157⁃164. DOI: 10.1016/j.jdermsci. 2004.08.012.
［28］	Fujii K, Yamamoto Y, Mizutani Y, et al. Indoleamine 2,3⁃dioxygenase 2 deficiency exacerbates imiquimod⁃induced psoriasis⁃like skin inflammation［J］. Int J Mol Sci, 2020,21（15）DOI: 10.3390/ijms21155515.
［29］	Choudhary V, Ajebo E, Uaratanawong R, et al. Loss of indoleamine⁃2,3⁃dioxygenase⁃1 （IDO1） in knockout mice does not affect the development of skin lesions in the imiquimod⁃induced mouse model of psoriasis［J］. Int J Tryptophan Res, 2022,15:11786469221078191. DOI: 10.1177/11786469221078191.
［30］	Elizei SS, Pakyari M, Ghoreishi M, et al. IDO⁃expressing fibroblasts suppress the development of imiquimod⁃induced psoriasis⁃like dermatitis［J］. Cell Transplant, 2018,27（3）:557⁃570. DOI: 10.1177/0963689718757482.
［31］	Wang M, Wang Y, Zhang M, et al. Kynureninase contributes to the pathogenesis of psoriasis through pro⁃inflammatory effect［J］. J Cell Physiol, 2022,237（1）:1044⁃1056. DOI: 10.1002/jcp. 30587.
［32］	Roberson ED, Liu Y, Ryan C, et al. A subset of methylated CpG sites differentiate psoriatic from normal skin［J］. J Invest Dermatol, 2012,132（3 Pt 1）:583⁃592. DOI: 10.1038/jid.2011.348.
［33］	Chiricozzi A, Guttman⁃Yassky E, Suárez⁃Fariñas M, et al. Integrative responses to IL⁃17 and TNF⁃α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis［J］. J Invest Dermatol, 2011,131（3）:677⁃687. DOI: 10.1038/jid. 2010.340.
［34］	Clement CC, D'Alessandro A, Thangaswamy S, et al. 3⁃Hydroxy⁃L⁃kynurenamine is an immunomodulatory biogenic amine［J］. Nat Commun, 2021,12（1）:4447. DOI: 10.1038/s41467⁃021⁃24785⁃3.
［35］	Salimi Elizei S, Poormasjedi⁃Meibod MS, Wang X, et al. Kynurenic acid downregulates IL⁃17/1L⁃23 axis in vitro［J］. Mol Cell Biochem, 2017,431（1⁃2）:55⁃65. DOI: 10.1007/s11010⁃017⁃2975⁃3.
［36］	Qiao P, Zhang C, Yu J, et al. Quinolinic acid, a tryptophan metabolite of the skin microbiota, negatively regulates NLRP3 inflammasome through AhR in psoriasis［J］. J Invest Dermatol, 2022,142（8）:2184⁃2193. DOI: 10.1016/j.jid.2022.01.010.
［37］	Spiera H, Lefkovits AM. Remission of psoriasis with low dietary tryptophan［J］. Lancet, 1967,2（7507）:137⁃139. DOI: 10.1016/s0140⁃6736（67）92970⁃4.
［38］	Petrozzi JW, Rosenbloom J. Low⁃tryptophan diet in treatment of psoriasis［J］. JAMA, 1968,205（6）:345⁃346.
［39］	Munder M. Arginase: an emerging key player in the mammalian immune system［J］. Br J Pharmacol, 2009,158（3）:638⁃651. DOI: 10.1111/j.1476⁃5381.2009.00291.x.
［40］	Bogdan C. Nitric oxide synthase in innate and adaptive immunity: an update［J］. Trends Immunol, 2015,36（3）:161⁃178. DOI: 10.1016/j.it.2015.01.003.
［41］	Mondanelli G, Bianchi R, Pallotta MT, et al. A relay pathway between arginine and tryptophan metabolism confers immunosuppressive properties on dendritic cells［J］. Immunity, 2017,46（2）:233⁃244. DOI: 10.1016/j.immuni.2017.01.005.
［42］	Pohla L, Ottas A, Kaldvee B, et al. Hyperproliferation is the main driver of metabolomic changes in psoriasis lesional skin［J］. Sci Rep, 2020,10（1）:3081. DOI: 10.1038/s41598⁃020⁃59996⁃z.
［43］	Kamleh MA, Snowden SG, Grapov D, et al. LC⁃MS metabolomics of psoriasis patients reveals disease severity⁃dependent increases in circulating amino acids that are ameliorated by anti⁃TNFα treatment［J］. J Proteome Res, 2015,14（1）:557⁃566. DOI: 10. 1021/pr500782g.
［44］	Hu X, Qi C, Feng F, et al. Combining network pharmacology, RNA⁃seq, and metabolomics strategies to reveal the mechanism of Cimicifugae Rhizoma ⁃ Smilax glabra Roxb herb pair for the treatment of psoriasis［J］. Phytomedicine, 2022,105:154384. DOI: 10.1016/j.phymed.2022.154384.
［45］	Wang H, Xie B, Lan L, et al. Metabolomics strategy of Pikang oral liquid in the treatment of psoriasis［J］. Biomed Chromatogr, 2023,37（6）:e5598. DOI: 10.1002/bmc.5598.
［46］	Bruch⁃Gerharz D, Schnorr O, Suschek C, et al. Arginase 1 overexpression in psoriasis: limitation of inducible nitric oxide synthase activity as a molecular mechanism for keratinocyte hyperproliferation［J］. Am J Pathol, 2003,162（1）:203⁃211. DOI: 10.1016/S0002⁃9440（10）63811⁃4.
［47］	Abeyakirthi S, Mowbray M, Bredenkamp N, et al. Arginase is overactive in psoriatic skin［J］. Br J Dermatol, 2010,163（1）:193⁃196. DOI: 10.1111/j.1365⁃2133.2010.09766.x.
［48］	Grzywa TM, Sosnowska A, Matryba P, et al. Myeloid cell⁃derived arginase in cancer immune response［J］. Front Immunol, 2020,11:938. DOI: 10.3389/fimmu.2020.00938.
［49］	Cao LY, Chung JS, Teshima T, et al. Myeloid⁃derived suppressor cells in psoriasis are an expanded population exhibiting diverse T⁃cell⁃suppressor mechanisms［J］. J Invest Dermatol, 2016,136（9）:1801⁃1810. DOI: 10.1016/j.jid.2016.02.816.
［50］	Hou Y, Zhang H, Zhu Y, et al. Targeting upregulation of the immunosuppressive activity of MDSCs with indirubin as a novel strategy to alleviate psoriasis［J］. Int Immunopharmacol, 2023,123:110710. DOI: 10.1016/j.intimp.2023.110710.
［51］	Köhler I, Bivik Eding C, Kasic NK, et al. NOS2⁃derived low levels of NO drive psoriasis pathogenesis［J］. Cell Death Dis, 2024,15（6）:449. DOI: 10.1038/s41419⁃024⁃06842⁃z.
［52］	Xu H, Zhang X, Wang X, et al. Cellular spermine targets JAK signaling to restrain cytokine⁃mediated autoimmunity［J］. Immunity, 2024,57（8）:1796⁃1811. DOI: 10.1016/j.immuni.2024. 05.025.
［53］	Wang MJ, Huang HJ, Xu YY, et al. Metabolic rewiring in keratinocytes by miR⁃31⁃5p identifies therapeutic intervention for psoriasis［J］. EMBO Mol Med, 2023,15（4）:e15674. DOI: 10. 15252/emmm.202215674.

[1]	Committee on Psoriasis, Chinese Society of Dermatology. Expert consensus on management of psoriasis with comorbidities （2026） [J]. Chinese Journal of Dermatology, 2026, 59(3): 193-207.
[2]	Wang Juncheng, Liu Jie. Artificial intelligence in psoriasis: diagnosis, treatment and patient management [J]. Chinese Journal of Dermatology, 2026, 0(3): 20240061-e20240061.
[3]	Chinese Society of Dermatology, China Dermatologist Association, Dermatology Branch of China International Exchange and Promotive Association for Medical and Health Care, Rare Skin Diseases Committee, China Alliance for Rare Diseases. Expert consensus on spesolimab in the treatment of inflammatory skin diseases （2026 edition） [J]. Chinese Journal of Dermatology, 2026, 59(2): 113-119.
[4]	Xue Tianping, Lu Zhenzhong, Wang Hongsheng. Relationship between the pathogenesis of psoriasis and microbial flora [J]. Chinese Journal of Dermatology, 2026, 59(1): 89-92.
[5]	Committee on Psoriasis, Chinese Society of Dermatology. Expert proposal on apremilast for the treatment of psoriasis （2025 edition） [J]. Chinese Journal of Dermatology, 2025, 58(5): 416-424.
[6]	Li Ziyu, Lu Yan. Paying attention to severe skin diseases after COVID-19 [J]. Chinese Journal of Dermatology, 2025, 58(4): 378-383.
[7]	Group on Pediatric Dermatology, China Dermatologist Association, Committee on Psoriasis, Chinese Society of Dermatology. Expert consensus on the diagnosis and treatment of pediatric pustular psoriasis in China （2025 version） [J]. Chinese Journal of Dermatology, 2025, 58(4): 297-306.
[8]	He Chunxia, Jin Hongzhong . Principles, current status, challenges and perspectives in the diagnosis and treatment of critical dermatological emergencies [J]. Chinese Journal of Dermatology, 2025, 58(4): 307-314.
[9]	Li Xiuzhen, Xu Xiulian. Effects of interleukin-23 inhibitors on psoriasis comorbidities [J]. Chinese Journal of Dermatology, 2025, 58(3): 268-272.
[10]	Lianghong Chen Yan SUN Jing-Yu WANG. Benvitimod for the treatment of dermatoses [J]. Chinese Journal of Dermatology, 2025, 58(3): 266-268.
[11]	Wang Yujue, Li Qingyang, Wang Gang. Role of vascular endothelial cells in the pathogenesis of psoriasis [J]. Chinese Journal of Dermatology, 2025, 0(3): 20250265-e20250265.
[12]	Ma Jing, Luan Chao, Chen Kun. Lipid metabolism-related proteins in psoriasis [J]. Chinese Journal of Dermatology, 2025, 0(3): 20220878-e20220878.
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Tryptophan and arginine metabolism in immune regulation and their role in the pathogenesis of psoriasis

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