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

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journal contribution
posted on 20.10.2020, 11:24 by Nikaïa Smith, Nicolas Pietrancosta, Sophia Davidson, Jacques Dutrieux, Lise Chauveau, Pasquale Cutolo, Michel Dy, Daniel Scott-Algara, Bénédicte Manoury, Onofrio Zirafi, Isabelle McCort-Tranchepain, Thierry Durroux, Françoise Bachelerie, Olivier Schwartz, Jan Münch, Andreas Wack, Sébastien Nisole, Jean-Philippe Herbeuval
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.