Novel Innate Receptor for the Fungal PAMP chitin

描述(申请人提供)：过敏性哮喘的炎性呼吸道反应可能是免疫细胞对环境因素(如空气中的真菌)调节失调的结果。该项目的长期目标是更好地了解Th2型(过敏性)呼吸道炎症的病理生理机制。长期接触这种真菌，交链孢霉，一直与过敏性呼吸道疾病的发展和恶化有关，如鼻炎、特应性哮喘和CRS。在鼻腔接触交链孢子、抗原和真菌细胞壁聚合物如甲壳素后，幼小鼠表现出明显的嗜酸性呼吸道炎症，Th2反应增强，呼吸道高反应性。尽管交链孢霉在过敏性呼吸道疾病的发生、发病和加重中的临床重要性已经得到了很好的证明，但对单个真菌产品/成分在这些病理状态中的作用知之甚少。真菌细胞壁聚合物甲壳素的重要性已在一定程度上被探索在炎症的背景下，并已被证明推动免疫反应有利于过敏性疾病的发展。我们发现了一种在肺上皮细胞中表达的甲壳素的新的候选受体。在这个探索性的项目中，我们将进一步了解几丁质如何与该受体结合，并开始利用肺上皮细胞和小鼠模型阐明该受体候选在先天免疫和变态反应性炎症反应中的作用。该项目的实施将有助于更好地了解持续性和复发性呼吸道炎症的机制，并可能导致开发更具体、有效的治疗和预防策略。

DESCRIPTION (provided by applicant): The inflammatory airway response in allergic asthma may be the result of immune cells that are dysregulated towards environmental factors such as airborne fungi. The long-term goal of this project is to better understand the pathophysiological mechanisms of Th2-type (allergic) airway inflammation. Exposure to the fungus, Alternaria, has long been implicated in the development and exacerbation of allergic airway disorders such as rhinitis, atopic asthma, and CRS. After intranasal exposure to Alternaria spores, antigens, and fungal cell wall polymers such as chitin, naive mice exhibit marked eosinophilic airway inflammation, enhanced Th2 responses, and airway hyperreactivity. Despite the well-documented clinical importance of Alternaria in the development, onset, and exacerbation of allergic airway diseases, little knowledge exists about the role of individual fungal products/components in theses pathological states. The importance of the fungal cell wall polymer chitin has been explored to some extent in the context of inflammation and has been shown to drive immune responses favoring the development of allergic disease. We have discovered a novel receptor candidate for chitin expressed in lung epithelial cells. In this exploratory project we will further our understanding of how chitin binds to this receptor and begin to elucidate the role of this receptor candidate in the context of innate immunity and allergic inflammatory responses using lung epithelial cells and mouse models. Execution of this project will lead to a better understanding of the mechanisms of persistent and recurrent airway inflammation and may lead to the development of more specific, effective therapies and prevention strategies.