Role of Mast Cells and Basophils in IgE Responses and in Allergic Airway Hyperresponsiveness
Role of Mast Cells and Basophils in IgE Responses and in Allergic Airway Hyperresponsiveness
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DOI：
10.4049/jimmunol.1101746
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发表时间：
2012-02-15
影响因子：
4.4
通讯作者：
Kubo, Masato
中科院分区：
文献类型：
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作者：
Sawaguchi, Minoru;Tanaka, Shinya;Kubo, Masato
我们建立了一个白喉毒素（DT）为基础的条件性缺失系统，使用114增强子元件先前被证明是特异性的肥大细胞（MC）或嗜碱性粒细胞（Mas-TRECK和Bas-TRECK小鼠）的IL-4的生产。DT治疗Bas-TRECK小鼠导致嗜碱性粒细胞的特异性缺失，而在Mas-TRECK小鼠中MC和嗜碱性粒细胞均缺失。DT处理的Mas-TRECK小鼠的被动皮肤过敏反应、IgE介导的被动全身过敏反应和IgE介导的慢性过敏性炎症受损，而DT处理的Bas-TRECK小鼠的IgE介导的慢性过敏性炎症受损。利用这些小鼠，我们还试图梳理出MC和嗜碱性粒细胞在气道高反应性（AHR）中的作用。虽然MC删除导致基础Ag特异性IgE水平略有增加，基础IgE水平显着增加，我们发现，这种删除显着损害AHR效应相，并伴有组胺水平下降。相比之下，嗜碱性粒细胞缺失对AHR效应期或对系统性OVA免疫诱导的IgE产生没有影响。我们的研究结果，使用这些新建立的Mas-TRECK和Bas-TRECK模型，证明了不可或缺的作用，MC作为效应细胞在AHR。免疫学杂志，2012，188：1809-1818。
We established a diphtheria toxin (DT)-based conditional deletion system using 114 enhancer elements previously shown to be specific for IL-4 production in mast cells (MCs) or basophils (Mas-TRECK and Bas-TRECK mice). DT treatment of Bas-TRECK mice resulted in specific deletion of basophils, whereas both MCs and basophils were deleted in Mas-TRECK mice. DT-treated Mas-TRECK mice had impaired passive cutaneous anaphylaxis, IgE-mediated passive systemic anaphylaxis, and IgE-mediated chronic allergic inflammation, whereas DT-treated Bas-TRECK mice had impaired IgE-mediated chronic allergic inflammation. Using these mice, we also sought to tease out the role of MCs and basophils in airway hyperresponsiveness (AHR). Although MC deletion resulted in a slight increase in basal Ag-specific IgE levels and significant increases in basal IgE levels, we found that this deletion markedly impaired the AHR effector phase and was accompanied by decreased histamine levels. By contrast, basophil deletion had no effect on the AHR effector phase or on IgE production induced by systemic OVA immunization. Our results, using these newly established Mas-TRECK and Bas-TRECK models, demonstrated an indispensable role for MCs as effector cells in AHR. The Journal of Immunology, 2012, 188: 1809-1818.