Absence of leukotriene B4 receptor 1 confers resistance to airway hyperresponsiveness and Th2-type immune responses
Absence of leukotriene B4 receptor 1 confers resistance to airway hyperresponsiveness and Th2-type immune responses
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DOI：
10.4049/jimmunol.175.7.4217
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发表时间：
2005-10-01
影响因子：
4.4
通讯作者：
Shimizu, T
中科院分区：
文献类型：
--
作者：
Terawaki, K;Yokomizo, T;Shimizu, T
哮喘是一种越来越常见的疾病，人们对其了解很少，也很难管理。该病的特点是呼吸道高反应性、慢性炎症和粘液过度产生。基于白三烯B-4受体1(BLT1)在Th2淋巴细胞中高表达的发现，我们利用OVA诱导的哮喘模型分析了BLT1的作用。BLT1基因缺失的小鼠没有出现呼吸道高反应性、嗜酸性炎症和杯状细胞增生。症状减轻的同时伴随着IgE产生的减少，以及支气管肺泡灌洗液中IL-5和IL-13的积累，这表明BLT1基因缺失的小鼠的Th2型免疫反应减弱。致敏的BLT1基因缺失小鼠外周淋巴结细胞在体外用抗原再次刺激后，其增殖和Th2细胞因子的产生明显减弱。因此，LTB4-BLT1轴是Th2型免疫反应发展所必需的，而通过BLT1阻断LTB4功能将在改善哮喘和相关的Th2偏向免疫疾病方面具有新颖和有用的作用。
Bronchial asthma is an increasingly common disorder that remains poorly understood and difficult to manage. The disease is characterized by airway hyperresponsiveness, chronic inflammation, and mucus overproduction. Based on the finding that leukotriene B-4 receptor 1 (BLT1) is expressed highly in Th2 lymphocytes, we analyzed the roles of BLT1 using an OVA-induced bronchial asthma model. BLT1-null mice did not develop airway hyperresponsiveness, eosinophilic inflammation, and hyperplasia of goblet cells. Attenuated symptoms were accompanied by reduced IgE production, and accumulation of IL-5 and IL-13 in bronchoalveolar lavage fluid, suggesting attenuated Th2-type immune response in BLT1-null mice. Peribronchial lymph node cells of sensitized BLT1-null mice showed much attenuated proliferation and production of Th2 cytokines upon re-stimulation with Ag in vitro. Thus, LTB4-BLT1 axis is required for the development of Th2-type immune response, and blockade of LTB4 functions through BLT1 would be novel and useful in the effort to ameliorate bronchial asthma and related Th2-biased immune disorders.