The H1 histamine receptor regulates allergic lung responses
The H1 histamine receptor regulates allergic lung responses
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DOI：
10.1172/jci26150
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发表时间：
2006-06-01
影响因子：
15.9
通讯作者：
Oettgen, Hans C.
中科院分区：
文献类型：
--
作者：
Bryce, Paul J.;Mathias, Clinton B.;Oettgen, Hans C.
组胺，通过1型受体（H1 R）的信号，已被证明可以抑制Th 2细胞因子的体外培养的T细胞的生产。我们使用小鼠哮喘模型研究了H1 R在体内过敏性炎症中的作用。致敏H1 R（-/-）小鼠的变应原刺激脾T细胞表现出增强的Th 2细胞因子产生。尽管存在这种Th 2偏好，过敏原攻击的H1 R（-/-）小鼠表现出肺部Th 2细胞因子mRNA水平降低、气道炎症、杯状细胞化生和气道高反应性（AHR）。通过鼻内IL-4或IL-13恢复H1 R（-/-）小鼠中的肺Th 2细胞因子恢复炎性肺应答和AHR进一步的研究表明，组胺作为T细胞趋化因子起作用，并且有缺陷的T细胞运输是导致肺部炎症不存在的原因。培养的T细胞在体外响应组胺而迁移，但这被阻断H1 R而不是H2 R消除。在体内，吸入过敏原激发后，过敏原特异性WT而不是H1 R（-/-）CD 4（+）T细胞被募集到幼稚受体的肺中。H1 R（-/-）细胞不能引起气道炎症或在转移WT T细胞后观察到的AHR。我们的数据确定了组胺和H1 R在促进Th 2细胞迁移到过敏原暴露部位中的作用。
Histamine, signaling via the type 1 receptor (H1R), has been shown to suppress Th2 cytokine production by in vitro cultured T cells. We examined the role of H1R in allergic inflammation in vivo using a murine asthma model. Allergen-stimulated splenic T cells from sensitized H1R(-/-) mice exhibited enhanced Th2 cytokine production. Despite this Th2 bias, allergen-challenged H1R(-/-) mice exhibited diminished lung Th2 cytokine mRNA levels, airway inflammation, goblet cell metaplasia, and airway hyperresponsiveness (AHR). Restoration of pulmonary Th2 cytokines in H1R(-/-) mice by intranasal IL-4 or IL-13 restored inflammatory lung responses and AHR Further investigation revealed that histamine acts as a T cell chemotactic factor and defective T cell trafficking was responsible for the absence of lung inflammation. Cultured T cells migrated in response to histamine in vitro, but this was ablated by blockade of H1R but not H2R In vivo, allergen-specific WT but not H1R(-/-) CD4(+) T cells were recruited to the lungs of naive recipients following inhaled allergen challenge. H1R(-/-) cells failed to confer airway inflammation or AHR observed after transfer of WT T cells. Our data establish a role for histamine and H1R in promoting the migration of Th2 cells into sites of allergen exposure.