The histamine H4-receptor (H4R) regulates eosinophilic inflammation in ovalbumin-induced experimental allergic asthma in mice
The histamine H4-receptor (H4R) regulates eosinophilic inflammation in ovalbumin-induced experimental allergic asthma in mice
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DOI：
10.1002/eji.201445179
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发表时间：
2015-04-01
影响因子：
5.4
通讯作者：
Neumann, Detlef
中科院分区：
文献类型：
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作者：
Hartwig, Christina;Munder, Antje;Neumann, Detlef
组胺通过组胺H-4受体（H4 R）促进小鼠实验性过敏性哮喘的发病。在致敏和激发期间应用H4 R拮抗剂可降低疾病的严重程度。然而，在实验性过敏性哮喘中功能性表达H4 R的特定细胞类型尚未在体内得到很好的表征。在这项研究中，我们确定了在实验性哮喘中负责H4 R活性的细胞类型和相关的生理机制。使用H4 R缺陷小鼠，我们研究了H4 R在致敏和效应阶段的作用。在体外致敏反应过程中缺乏H4 R表达的DC导致效应T细胞在体内过继转移后不能诱导肺中的整个嗜酸性炎症。缺乏H4 R表达的小鼠，其过继转移有在H4 R +/+ DC存在下极化的H4 R +/+ T细胞，表现出减少的炎症体征和改善的肺功能。在这里，我们提供了在体内的证据表明，在实验性哮喘小鼠的H4 R特异性调节致敏过程中的DC的激活，而在效应相的H4 R是活跃的细胞参与嗜酸性粒细胞的激活，并可能其他细胞。针对H4 R的假定疗法可能是发展为IL-5依赖性嗜酸性粒细胞增多症的哮喘患者的一种选择。
Via the histamine H-4-receptor (H4R), histamine promotes the pathogenesis of experimental allergic asthma in mice. Application of H4R antagonists during sensitization as well as during provocation reduces the severity of the disease. However, the specific cell types functionally expressing H4R in experimental allergic asthma have not been well characterized in vivo. In this study, we identified the cell type(s) responsible for H4R activity in experimental asthma and related physiological mechanisms. Using H4R-deficient mice, we studied the role of H4R in the sensitization and effector phase. DCs lacking H4R expression during the in vitro sensitization reaction resulted in effector Tcells unable to induce an entire eosinophilic inflammation in the lung upon adoptive transfer in vivo. Recipient mice lacking H4R expression, which were adoptively transferred with H4R+/+ Tcells polarized in the presence of H4R+/+ DCs, showed reduced signs of inflammation and ameliorated lung function. Here, we provide in vivo evidence that in experimental asthma in mice the H4R specifically regulates activation of DCs during sensitization, while in the effector phase the H4R is active in cells involved in the activation of eosinophils, and possibly other cells. A putative therapy targeting the H4R may be an option for asthma patients developing IL-5-dependent eosinophilia.