Histamine polarizes human dendritic cells into Th2 cell-promoting effector dendritic cells.
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-gamma, 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.
Caron
G
G
Centre d'Immunologie Pierre Fabre, 5 avenue Napoléon III, 74164 Saint Julien en Genevois, France.
Delneste
Y
Y
Roelandts
E
E
Duez
C
C
Bonnefoy
J Y
JY
Pestel
J
J
Jeannin
P
P
D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D008070:Lipopolysaccharides; D018664:Interleukin-12; D006632:Histamine; D007371:Interferon-gamma