1. Natural amines inhibit activation of human plasmacytoid dendritic cells through CXCR4 engagement.
- Author
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Smith N, Pietrancosta N, Davidson S, Dutrieux J, Chauveau L, Cutolo P, Dy M, Scott-Algara D, Manoury B, Zirafi O, McCort-Tranchepain I, Durroux T, Bachelerie F, Schwartz O, Münch J, Wack A, Nisole S, and Herbeuval JP
- Subjects
- Ammonium Compounds chemistry, Animals, Dendritic Cells drug effects, HIV drug effects, HIV physiology, Histamine chemistry, Histamine pharmacology, Humans, Imidazoles pharmacology, Interferon Type I metabolism, Mice, Orthomyxoviridae physiology, Receptors, Histamine metabolism, TNF-Related Apoptosis-Inducing Ligand pharmacology, Thiourea analogs & derivatives, Thiourea pharmacology, Amines pharmacology, Dendritic Cells metabolism, Receptors, CXCR4 metabolism
- 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.
- Published
- 2017
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