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Abstract：
Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing the spliceosome, osteoclast differentiation, and coagulation pathways. Utilizing a specific inhibitor and gene-deficient mice, we demonstrate that STAT6 is required for mycosis-induced sinus inflammation. These findings confirm the relevance of this new model and portend future studies that further extend our understanding of the immunopathologic basis of airway mycosis and unified airway disease.
摘要：
统一气道疾病，包括并发哮喘和慢性鼻窦炎（CRS），是一种常见的，但对疾病了解甚少，没有治愈性治疗选择。建立小鼠慢性统一嗜酸性粒细胞气道炎症模型,用黑曲霉攻击小鼠，并通过免疫组织化学评估鼻窦粘膜和肺组织，流式细胞术,和基因表达。吸入尼日尔分生孢子会导致Th2偏向的肺和鼻窦炎症，这是过敏性哮喘和CRS的典型代表。与人类疾病相关的基因网络和通路分析不仅上调JAK-STAT和辅助性T细胞通路，但也有较少预期的控制剪接体的途径，破骨细胞分化，和凝血途径。利用特定的抑制剂和基因缺陷的小鼠，我们证明STAT6是真菌病诱导的鼻窦炎症所必需的.这些发现证实了这种新模型的相关性，并预示着未来的研究将进一步扩展我们对气道真菌病和统一气道疾病的免疫病理学基础的理解。
