Histamine Polarizes Human Dendritic Cells into Th2 Cell-Promoting Effector Dendritic Cells

• Published in: The Journal of immunology (1950) Vol. 167; no. 7; pp. 3682 - 3686
• Main Authors: Caron, Gersende, Delneste, Yves, Roelandts, Edith, Duez, Catherine, Bonnefoy, Jean-Yves, Pestel, Joel, Jeannin, Pascale
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.10.2001
• Subjects: Cell Differentiation; Cells, Cultured; Dendritic Cells - drug effects; Dendritic Cells - immunology; Histamine - pharmacology; Humans; Hypersensitivity - immunology; Interferon-gamma - biosynthesis; Interleukin-12 - biosynthesis; Lipopolysaccharides - pharmacology; Myeloid Progenitor Cells - drug effects; Myeloid Progenitor Cells - immunology; Th2 Cells - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.7.3682

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-γ, 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.