最新研究发现，毛细淋巴管生成对气道炎症刺激敏感且是某些炎症性疾病进程的强有力参与者。我们的研究显示，鼻息肉上皮细胞在低氧条件下发生以IL-17A表达减少为特征的异常黏膜免疫应答，同时黏膜下淋巴管密度减少，血管通透性增强，提示鼻息肉黏膜对低氧等炎症刺激具有独特的病理生理学机制，而淋巴管生成及其功能异常可能是鼻息肉发病乃至高复发率的关键。课题拟行：①免疫荧光、RT-PCR、蛋白芯片等明确鼻息肉组织中VEGF/VEGFR3/Ang/Tie2途径介导的淋巴管生成与功能异常相关调节因子；②体外检测淋巴管内皮细胞经相关因子诱导后免疫活性变化，确定诱导后LECs对DC、Eos、Mon/M细胞的免疫学功能的调控及途径；③体内实验明确该途径在鼻息肉发病中的作用；④Massarry、ELISA、流式等检测相关因子表观遗传变化并干预。揭示鼻息肉发病中淋巴管生成与功能障碍及其免疫调节机制，寻找鼻息肉治疗新靶点。

Lymphatic system plays an important role in the initiation of immune responses. The mechanism involved in the pathogenesis of nasal polyposis is far from clear. Recent evidences have shown that lymphangioenesis and dysfuction takes a key part in edema and inflammation of airway diseases. Our recent research results suggested that, hypoxia regulates IL-17a secretion from NP, and decreased lymph vessel density in sub-mucosa. Therefore, we propose lymphangioenesis and dysfuction play a key role in the pathogenesis of NP, even the high recurrence.Concrete research contents include: ①analyze the lymphangioenesis and dysfuction in NP by using immunofluorescence,RT - PCR and protein microarray, screen out associated factors.②detect the activity of Lymphatic endothelial cells induced by the associated factors, and the correlation between LECs and DC、Eos、Mon/M.③animal models will be performed to test the associated way in vivo.④induce associated factors demethylation in vitro by using demethyl-agent.Massarry, ELISA and FACS will be performed to test whether epigenetics modified could alter the process of NP. The project will explain the pathogenesis of NP from lymphatic perspective,even the high recurrence.Future NP therapies target might be exploited and intervened using epigenetic method.