Centre de Recherche de L'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada.
Curr Opin Allergy Clin Immunol. 2012 Oct;12(5):467-74. doi: 10.1097/ACI.0b013e328357cc17.
In recent years, considerable effort has been invested in developing mouse models of allergic airway disease, as a means of evaluating the role of select genes in its pathophysiology. Here, we review the principal models used in this field, including models of allergic asthma and hypersensitivity pneumonitis. As an example of how these models can reveal novel functional roles for genes, we review our work showing a role for the stem-cell-associated gene, Cd34. Through this example, we illustrate the genetic and immunological strategies available in the field to better understand allergic airway inflammation.
CD34 was found to play an important role in the development of two different models of allergic disease, that is, Th2-driven allergic asthma and Th17-driven hypersensitivity pneumonitis. Using a combination of genetically modified mice as well as cell transfers and chimeric mice, we showed that CD34 is important for the efficient trafficking of hematopoietic subsets into and out of the lung, including mast cells, eosinophils and dendritic cells.
The currently available array of mutant mice and animal models of allergic disease now offers an opportunity to make profound insights into these diseases and provide preclinical models for the development of therapeutics.
近年来,人们投入了相当大的精力来开发过敏性气道疾病的小鼠模型,作为评估特定基因在其病理生理学中作用的一种手段。在这里,我们回顾了该领域中使用的主要模型,包括过敏性哮喘和过敏性肺炎模型。作为这些模型如何揭示基因新的功能作用的一个例子,我们回顾了我们的工作,表明干细胞相关基因 Cd34 发挥作用。通过这个例子,我们说明了该领域中可用的遗传和免疫策略,以更好地理解过敏性气道炎症。
发现 Cd34 在两种不同的过敏性疾病模型(即 Th2 驱动的过敏性哮喘和 Th17 驱动的过敏性肺炎)的发展中起着重要作用。我们使用基因修饰小鼠以及细胞转移和嵌合小鼠的组合,表明 CD34 对于造血细胞亚群在肺部内外的有效迁移很重要,包括肥大细胞、嗜酸性粒细胞和树突状细胞。
目前可用的突变小鼠和过敏性疾病动物模型为深入了解这些疾病并为治疗药物的开发提供临床前模型提供了机会。