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Nat Commun. 2017 Feb 9;8:14253. doi: 10.1038/ncomms14253.

Natural amines inhibit activation of human plasmacytoid dendritic cells through CXCR4 engagement.

Author information

  • 1CNRS UMR-8601, Université Paris Descartes, CICB, 45 rue des Saints-Pères, 75006 Paris, France.
  • 2Team Chemistry &Biology, Modeling &Immunology for Therapy, CBMIT.
  • 3Immunoregulation Laboratory, Francis Crick Institute, London NW1 1AT, UK.
  • 4INSERM UMR-S 1124, Université Paris Descartes, 45 rue des Saints-Pères, 75006 Paris, France.
  • 5Institut Pasteur, Virus &Immunity Unit, 25-28 Rue du Dr Roux, Paris 75015, France.
  • 6Inflammation Chimiokines et Immunopathologie, INSERM, Faculté de médecine-Université Paris-Sud, Université Paris-Saclay, 92140 Clamart, France.
  • 7CNRS UMR-8147, Hôpital Necker, 156 Rue de Vaugirard, 75015 Paris, France.
  • 8Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25-28 Rue du Dr Roux, Paris 75015, France.
  • 9INSERM U1151, CNRS8253, Université Paris Descartes, Hôpital Necker, 156 Rue de Vaugirard, 75015 Paris, France.
  • 10Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany.
  • 11Institut de Génomique Fonctionnelle, CNRS UMR5203, INSERM U661, Université de Montpellier (IFR3), 141 rue de la Cardonille, F-34094 Montpellier Cedex 5, France.

Abstract

Plasmacytoid dendritic cells (pDC) are specialized in secretion of type I interferon in response to pathogens. Here we show that natural monoamines and synthetic amines inhibit pDC activation by RNA viruses. Furthermore, a synthetic analogue of histamine reduces type I interferon production in a mouse model of influenza infection. We identify CXC chemokine receptor 4 (CXCR4) as a receptor used by amines to inhibit pDC. Our study establishes a functional link between natural amines and the innate immune system and identifies CXCR4 as a potential 'on-off' switch of pDC activity with therapeutic potential.

PMID:
28181493
DOI:
10.1038/ncomms14253
[PubMed - in process]
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