title: The histamine H4 -receptor (H4 R) regulates eosinophilic inflammation in ovalbumin-induced experimental allergic asthma in mice.
abstract: Via the histamine H4 -receptor (H4 R), histamine promotes the pathogenesis of experimental allergic asthma in mice. Application of H4 R antagonists during sensitization as well as during provocation reduces the severity of the disease. However, the specific cell types functionally expressing H4 R in experimental allergic asthma have not been well characterized in vivo. In this study, we identified the cell type(s) responsible for H4 R activity in experimental asthma and related physiological mechanisms. Using H4 R-deficient mice, we studied the role of H4 R in the sensitization and effector phase. DCs lacking H4 R expression during the in vitro sensitization reaction resulted in effector T cells unable to induce an entire eosinophilic inflammation in the lung upon adoptive transfer in vivo. Recipient mice lacking H4 R expression, which were adoptively transferred with H4 R(+/+) T cells polarized in the presence of H4 R(+/+) DCs, showed reduced signs of inflammation and ameliorated lung function. Here, we provide in vivo evidence that in experimental asthma in mice the H4 R specifically regulates activation of DCs during sensitization, while in the effector phase the H4 R is active in cells involved in the activation of eosinophils, and possibly other cells. A putative therapy targeting the H4 R may be an option for asthma patients developing IL-5-dependent eosinophilia.
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Hannover, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Hartwig
authors.forename: Antje
authors.initials: A
authors.lastname: Munder
authors.forename: Silke
authors.initials: S
authors.lastname: Glage
authors.forename: Dirk
authors.initials: D
authors.lastname: Wedekind
authors.forename: Heiko
authors.initials: H
authors.lastname: Schenk
authors.forename: Roland
authors.initials: R
authors.lastname: Seifert
authors.forename: Detlef
authors.initials: D
authors.lastname: Neumann
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D039521:CD11c Antigen / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D006632:Histamine / Q000378:metabolism; D007249:Inflammation / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D008168:Lung / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D011968:Receptors, Histamine / Q000235:genetics / Q000276:immunology*; D000074040:Receptors, Histamine H4; D018418:Th2 Cells / Q000276:immunology / Q000637:transplantation
chemical_list: D000485:Allergens; D039521:CD11c Antigen; D016207:Cytokines; C498829:Hrh4 protein, mouse; D015848:Interleukin-5; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D006632:Histamine; D010047:Ovalbumin
keywords: Adoptive cell transfer; Dendritic cells; Experimental allergic asthma; Histamine H4-receptor (H4R); Inflammation; Ovalbumin; T cells