3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine
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Published:2021-07-21
Issue:1
Volume:12
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Clement Cristina C., D’Alessandro Angelo, Thangaswamy Sangeetha, Chalmers Samantha, Furtado RaquelORCID, Spada Sheila, Mondanelli Giada, Ianni Federica, Gehrke Sarah, Gargaro MarcoORCID, Manni Giorgia, Cara Luisa Carlota Lopez, Runge Peter, Tsai Wanxia Li, Karaman SinemORCID, Arasa Jorge, Fernandez-Rodriguez RubenORCID, Beck Amanda, Macchiarulo Antonio, Gadina Massimo, Halin CorneliaORCID, Fallarino FrancescaORCID, Skobe MihaelaORCID, Veldhoen MarcORCID, Moretti SimoneORCID, Formenti SilviaORCID, Demaria SandraORCID, Soni Rajesh K., Galarini Roberta, Sardella Roccaldo, Lauvau GregoireORCID, Putterman Chaim, Alitalo KariORCID, Grohmann UrsulaORCID, Santambrogio LauraORCID
Abstract
AbstractTryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-l-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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