3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine Clement, Cristina C. López Cara, Luisa Carlota The work was supported by the following grants: NIH-AG045223 and NIH-AI137198 to L.S.; the Swiss National Science Foundation, grant 310030_182528 to C.H.; Telethon GGP17094 and the Associazione Italiana per la Ricerca sul Cancro (AIRC; 19903) to F.F.; Sigrid Juselius Foundation to K.A.; NIH T32 DK007110 to S.C.; NIH-AI103338 and NIH-AI138552 to G.L.; NIH K12 GM102779/BETTR program to R.F.; Associazione Italiana per la Ricerca sul Cancro (AIRC 2019-23084) to U.G.; The Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases ZIG AR041181-11) to W.L.T. and M.G. European Union H2020 ERA project (No. 667824 -EXCELLtoINNOV) to M.V. Tryptophan 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. 2021-09-23T10:18:17Z 2021-09-23T10:18:17Z 2021-07-21 journal article Clement, C.C... [et al.]. 3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine. Nat Commun 12, 4447 (2021). [https://doi.org/10.1038/s41467-021-24785-3] http://hdl.handle.net/10481/70398 10.1038/s41467-021-24785-3 eng info:eu-repo/grantAgreement/EC/H2020/667824 http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España Nature