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Centre d’Immunologie Pierre Fabre, Saint Julien en Genevois, France;
Institut National de la Santé et de la Recherche Médicale, Unité 416, Institut Pasteur, Lille, France;
Pharmacie Centrale, Centre Hospitalier, Hazebrouck, France
Allergic disorders are characterized by allergen-specific
Th2-biased responses. Signals controlling Th2 cell polarization,
especially those acting by polarizing dendritic cells (DC) into
Th2-promoting DC (DC2), are not well known. Histamine, a mediator
released by allergen-stimulated mast cells from allergic subjects, has
been reported to activate human immature DC. We have therefore tested
whether histamine affects DC polarization. We report here that
histamine inhibits LPS-induced IL-12 production and polarizes
uncommitted maturing DC into effector DC2. DC matured in the presence
of histamine fail to produce IL-12 upon subsequent stimulation and
prime Th2 responses, even in presence of IFN-
, a potent DC1-driving
factor. All these effects are mediated through both H1 and H2
receptors. These data show that histamine is a potent DC2-polarizing
factor and provide evidence for a novel mechanism that explains the
initiation and maintenance of a predominant Th2 response in allergic
disorders.
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