3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine

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Clement , C C , D'Alessandro , A , Thangaswamy , S , Chalmers , S , Furtado , R , Spada , S , Mondanelli , G , Ianni , F , Gehrke , S , Gargaro , M , Manni , G , Lopez Cara , L C , Runge , P , Tsai , W L , Karaman , S , Arasa , J , Fernandez-Rodriguez , R , Beck , A , Macchiarulo , A , Gadina , M , Halin , C , Fallarino , F , Skobe , M , Veldhoen , M , Moretti , S , Formenti , S , Demaria , S , Soni , R K , Galarini , R , Sardella , R , Lauvau , G , Putterman , C , Alitalo , K , Grohmann , U & Santambrogio , L 2021 , ' 3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine ' , Nature Communications , vol. 12 , no. 1 , 4447 . https://doi.org/10.1038/s41467-021-24785-3

Title: 3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine
Author: Clement, Cristina C.; D'Alessandro, Angelo; Thangaswamy, Sangeetha; Chalmers, Samantha; Furtado, Raquel; Spada, Sheila; Mondanelli, Giada; Ianni, Federica; Gehrke, Sarah; Gargaro, Marco; Manni, Giorgia; Lopez Cara, Luisa Carlota; Runge, Peter; Tsai, Wanxia Li; Karaman, Sinem; Arasa, Jorge; Fernandez-Rodriguez, Ruben; Beck, Amanda; Macchiarulo, Antonio; Gadina, Massimo; Halin, Cornelia; Fallarino, Francesca; Skobe, Mihaela; Veldhoen, Marc; Moretti, Simone; Formenti, Silvia; Demaria, Sandra; Soni, Rajesh K.; Galarini, Roberta; Sardella, Roccaldo; Lauvau, Gregoire; Putterman, Chaim; Alitalo, Kari; Grohmann, Ursula; Santambrogio, Laura
Contributor organization: INDIVIDRUG - Individualized Drug Therapy
Organotypic Vasculature Lab
CAN-PRO - Translational Cancer Medicine Program
Research Programs Unit
Kari Alitalo / Principal Investigator
Date: 2021-07-21
Language: eng
Number of pages: 17
Belongs to series: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-021-24785-3
URI: http://hdl.handle.net/10138/334415
Abstract: 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-gamma mediated STAT1/NF-kappa Beta 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-1 beta, IFN-gamma, 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. 3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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