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
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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