IL-31在慢性鼻窦炎伴鼻息肉黏膜组织重塑中的作用与机制研究

组织重塑是慢性鼻窦炎伴鼻息肉(CRSwNP)的重要特征，与炎症类型相关。嗜酸性粒细胞性鼻息肉（ECRSwNP）以Th2炎症为主，为临床治疗难点。ECRSwNP中与Th2细胞相关的黏膜重塑机制尚未阐明。我们前期研究发现白细胞介素（IL）-31在ECRSwNP表达显著增高；80%的Th2细胞表达IL-31；IL-31体外刺激鼻黏膜上皮细胞可上调IL-31受体IL-31RA和OSMR表达，激活JAK/STAT信号通路中的关键分子，促进下游组织重塑因子MUC5AC和基质金属蛋白酶表达。据此提出假设：IL-31作为连接炎性细胞和上皮细胞的重要因子，在CRSwNP组织重塑中发挥作用。本课题以鼻黏膜上皮细胞和动物模型为研究对象，构建IL-31过表达及敲减腺病毒，应用免疫学及分子生物学技术，探索IL-31在CRSwNP组织重塑中的作用和机制。本研究对丰富CRSwNP发病机制有重要意义，可为治疗提供新靶点。

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by marked tissue remodeling, which associates with inflammation patterns. Eosinophilic CRSwNP (ECRSwNP) is a challenging endotype with frequent recurrence resulting from the biased Th2 inflammation. Mucosal remodeling mechanisms in ECRSwNP, correlating with Th2 cells, remains unknown. In our preliminary experiments, we observed that the protein and mRNA levels of interleukin (IL)-31 increased significantly in ECRSwNP, compared to non-ECRSwNP, while 80% of Th2 cells expressed IL-31. Furthermore, when stimulated by IL-31 in vitro, nasal epithelium cells upregulated the expression of IL-31 receptors (IL-31RA and oncostatin M receptor), activated key molecules in Janus kinase/signal transducer and activator of transcription signal pathway, and promoted the production of matrix metalloproteinases and MUC5AC. Accordingly, we hypothesize that, as a link between inflammatory cells and epithelium cells, IL-31 play important role(s) in the mechanisms of tissue remodeling in CRSwNP. The proposed study will construct adenovirus mediated overexpression or knock-down of IL-31 to explore the function of IL-31 and its udnerlying mechanisms in mucosal remodeling. Epithelium from nasal mucosa and CRS animal model will be studied by immunology and molecular biology techniques. We anticipate this study will shed light on remodeling mechanism(s) underlying CRSwNP and provide potential target for better treatment.