Histamine polarizes human dendritic cells into Th2 cell-promoting effectordendritic cells

Allergic disorders are characterized by allergen-specific Th2-biased respon ses. Signals controlling Th2 cell polarization, especially those acting by polarizing dendritic cells (DC) into Th2-promoting DC (DC2), are not well k nown. Histamine, a mediator released by allergen-stimulated mast cells from allergic subjects, has been reported to activate human immature DC. We hav e therefore tested whether histamine affects DC polarization. We report her e that histamine inhibits LPS-induced IL-12 production and polarizes uncomm itted maturing DC into effector DC2. DC matured in the presence of histamin e fail to produce IL-12 upon subsequent stimulation and prime Th2 responses , even in presence of IFN-gamma, a potent DC1-driving factor. All these eff ects are mediated through both H1 and H2 receptors. These data show that hi stamine 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.