The histamine H 4 ‐receptor (H 4 R) regulates eosinophilic inflammation in ovalbumin‐induced experimental allergic asthma in mice

• Published in: European journal of immunology 2015-04, Vol.45 (4), p.1129-1140
• Main Authors: Hartwig, Christina, Munder, Antje, Glage, Silke, Wedekind, Dirk, Schenk, Heiko, Seifert, Roland, Neumann, Detlef
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201445179

Via the histamine H 4 ‐receptor (H 4 R), histamine promotes the pathogenesis of experimental allergic asthma in mice. Application of H 4 R antagonists during sensitization as well as during provocation reduces the severity of the disease. However, the specific cell types functionally expressing H 4 R in experimental allergic asthma have not been well characterized in vivo. In this study, we identified the cell type(s) responsible for H 4 R activity in experimental asthma and related physiological mechanisms. Using H 4 R‐deficient mice, we studied the role of H 4 R in the sensitization and effector phase. DCs lacking H 4 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 H 4 R expression, which were adoptively transferred with H 4 R +/+ T cells polarized in the presence of H 4 R +/+ DCs, showed reduced signs of inflammation and ameliorated lung function. Here, we provide in vivo evidence that in experimental asthma in mice the H 4 R specifically regulates activation of DCs during sensitization, while in the effector phase the H 4 R is active in cells involved in the activation of eosinophils, and possibly other cells. A putative therapy targeting the H 4 R may be an option for asthma patients developing IL‐5‐dependent eosinophilia.