Engagement of Nuclear Coactivator 7 by 3-Hydroxyanthranilic Acid Enhances Activation of Aryl Hydrocarbon Receptor in Immunoregulatory Dendritic Cells
Autor: | Maria Teresa Pallotta, Ciriana Orabona, Marco Gargaro, Elisa Proietti, Eleonora Panfili, Ioana Maria Iamandii, Emilia Maria Cristina Mazza, Giorgia Manni, Violetta Cecchetti, Maria Laura Belladonna, Carmine Vacca, Serena Massari, Ursula Grohmann, Silvio Bicciato, Oriana Tabarrini, Davide Matino, Roberta Bianchi, Paolo Puccetti, Francesca Fallarino, Alberta Iacono, Giulia Scalisi, Claudia Volpi, Giada Mondanelli |
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Rok vydání: | 2019 |
Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Kynurenine pathway Immune regulation dendritic cell 3-Hydroxyanthranilic Acid Nuclear Receptor Coactivators Immunology aryl hydrocarbon (Ah) receptor Lymphocyte Activation T-Lymphocytes Regulatory immune regulation nuclear coactivator 7 (NCOA7) tryptophan metabolism 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Immune system Coactivator Immunology and Allergy Animals Humans 3-Hydroxyanthranilic acid Tryptophan metabolism Aryl hydrocarbon (Ah) receptor Kynurenine Original Research Tumor microenvironment biology FOXP3 Dendritic cell Dendritic Cells Aryl hydrocarbon receptor Nuclear coactivator 7 (NCOA7) Cell biology Mice Inbred C57BL 030104 developmental biology chemistry Receptors Aryl Hydrocarbon biology.protein Female lcsh:RC581-607 030215 immunology |
Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 10 (2019) |
ISSN: | 1664-3224 |
Popis: | Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first step in the kynurenine pathway of tryptophan (Trp) degradation that produces several biologically active Trp metabolites. L-kynurenine (Kyn), the first byproduct by IDO1, promotes immunoregulatory effects via activation of the Aryl hydrocarbon Receptor (AhR) in dendritic cells (DCs) and T lymphocytes. We here identified the nuclear coactivator 7 (NCOA7) as a molecular target of 3-hydroxyanthranilic acid (3-HAA), a Trp metabolite produced downstream of Kyn along the kynurenine pathway. In cells overexpressing NCOA7 and AhR, the presence of 3-HAA increased the association of the two molecules and enhanced Kyn-driven, AhR-dependent gene transcription. Physiologically, conventional (cDCs) but not plasmacytoid DCs or other immune cells expressed high levels of NCOA7. In cocultures of CD4+ T cells with cDCs, the co-addition of Kyn and 3-HAA significantly increased the induction of Foxp3+ regulatory T cells and the production of immunosuppressive transforming growth factor β in an NCOA7-dependent fashion. Thus, the co-presence of NCOA7 and the Trp metabolite 3-HAA can selectively enhance the activation of ubiquitary AhR in cDCs and consequent immunoregulatory effects. Because NCOA7 is often overexpressed and/or mutated in tumor microenvironments, our current data may provide evidence for a new immune check-point mechanism based on Trp metabolism and AhR. |
Databáze: | OpenAIRE |
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