TY - JOUR
T1 - 3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine
AU - Clement, Cristina C.
AU - D’Alessandro, Angelo
AU - Thangaswamy, Sangeetha
AU - Chalmers, Samantha
AU - Furtado, Raquel
AU - Spada, Sheila
AU - Mondanelli, Giada
AU - Ianni, Federica
AU - Gehrke, Sarah
AU - Gargaro, Marco
AU - Manni, Giorgia
AU - Cara, Luisa Carlota Lopez
AU - Runge, Peter
AU - Tsai, Wanxia Li
AU - Karaman, Sinem
AU - Arasa, Jorge
AU - Fernandez-Rodriguez, Ruben
AU - Beck, Amanda
AU - Macchiarulo, Antonio
AU - Gadina, Massimo
AU - Halin, Cornelia
AU - Fallarino, Francesca
AU - Skobe, Mihaela
AU - Veldhoen, Marc
AU - Moretti, Simone
AU - Formenti, Silvia
AU - Demaria, Sandra
AU - Soni, Rajesh K.
AU - Galarini, Roberta
AU - Sardella, Roccaldo
AU - Lauvau, Gregoire
AU - Putterman, Chaim
AU - Alitalo, Kari
AU - Grohmann, Ursula
AU - Santambrogio, Laura
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-021-24785-3
DO - 10.1038/s41467-021-24785-3
M3 - Article
C2 - 34290243
AN - SCOPUS:85111000066
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4447
ER -