Institute of Integrative Biology, Molecular Biomedicine, ETH Zurich, Wagistrasse 27, 8952 Schlieren-Zurich, Switzerland.
Eur Respir J. 2012 Feb;39(2):429-38. doi: 10.1183/09031936.00197810. Epub 2011 Aug 4.
Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the "immunomodulatory barrier" of the airway epithelium. To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 μg endotoxin-free ovalbumin in conjunction with naphthalene-induced Clara cell depletion. Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung. These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.
变应性哮喘的发展是一个涉及免疫、神经元和组织细胞的复杂过程。在肺部，Clara 细胞代表气道上皮“免疫调节屏障”的主要部分。为了了解这些细胞对哮喘炎症结果的贡献，使用无佐剂卵白蛋白模型评估疾病的发展。用皮下注射 10μg 无内毒素卵白蛋白与萘诱导的 Clara 细胞耗竭相结合，使小鼠致敏。肺部 Clara 上皮细胞耗竭强烈减少嗜酸性粒细胞浸润，这与嗜酸性粒细胞趋化因子水平降低相关，此外，还减弱了 Th2 型炎症反应，包括白细胞介素 (IL)-4、IL-5 和 IL-13。相反，气道高反应性增加。进一步的研究表明，Clara 细胞是肺部嗜酸性粒细胞趋化因子的主要来源。这些发现首次表明，Clara 气道上皮细胞大量参与嗜酸性粒细胞趋化因子反应性 CCR3+免疫细胞的浸润，并增强肺部的变应性免疫反应。本研究将 Clara 细胞确定为炎症性肺部疾病（如变应性哮喘）的潜在治疗靶点。
