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

Cristina C. Clement, Angelo D’Alessandro, Sangeetha Thangaswamy, Samantha Chalmers, Raquel Furtado, Sheila Spada, Giada Mondanelli, Federica Ianni, Sarah Gehrke, Marco Gargaro, Giorgia Manni, Luisa Carlota Lopez Cara, Peter Runge, Wanxia Li Tsai, Sinem Karaman, Jorge Arasa, Ruben Fernandez-Rodriguez, Amanda Beck, Antonio Macchiarulo, Massimo GadinaCornelia Halin, Francesca Fallarino, Mihaela Skobe, Marc Veldhoen, Simone Moretti, Silvia Formenti, Sandra Demaria, Rajesh K. Soni, Roberta Galarini, Roccaldo Sardella, Gregoire Lauvau, Chaim Putterman, Kari Alitalo, Ursula Grohmann, Laura Santambrogio

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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-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.

Original languageEnglish (US)
Article number4447
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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