慢性阻塞性肺疾病（COPD）是香烟诱发持续的免疫炎症导致气道重塑和肺部损伤的疾病。新近研究发现COPD患者肺部分泌IL-17的NCR阴性天然淋巴细胞亚群3（NCR-ILC3）数量增多；我们的预实验发现在香烟诱导COPD小鼠肺部该细胞增多，并与肺气肿程度正相关。由此我们假设NCR-ILC3参与COPD/肺气肿的发生，拟通过香烟诱导COPD小鼠研究NCR-ILC3对COPD肺部病理改变的影响；分离原代NCR-ILC3细胞与香烟提取物共培养，研究香烟对NCR-ILC3的影响；分离原代气道上皮细胞与NCR-ILC3共培养，并阻断上皮细胞内IL-17受体下游的Act1/TRAF6/NF-kB和Act1/TRAF6/p38MAPK通路，探讨在两种细胞共存的微环境下NCR-ILC3对气道上皮细胞的影响及机制。本研究能更深入了解肺部黏膜固有免疫在COPD发生中的作用，有助于阻止COPD肺部免疫损伤的发生。

Chronic obstructive pulmonary disease (COPD) is cigarette-induced and immune-related inflammatory disease, which leads to airway remodeling and pulmonary damage. Recent study found an increased number of NCR negative innate lymphoid cells 3 (ILC3), a novel innate immunocyte that secrets IL-17, in the pulmonary of COPD patients when compared with controls. Moreover, in our pilot study, we found that the number of NCR-ILC3 in pulmonary was higher in cigarette-induced COPD mice than that in control, which was positively correlated with alveolar destruction. Thus, we suppose that NCR-ILC3 may contribute to COPD/emphysema development. This present study will investigate the relationship between NCR-ILC3 number and pathologic change of lung based on cigarette-induced COPD mice. The primary NCR-ILC3 will be isolated from mice lung and stimulated with cigarette smoke extract (CSE), aiming to study the effect of CSE on NCR-ILC3. We will further isolate primary airway epithelial cells and culture them with the primary NCR-ILC3, and then inhibit the downstream of IL-17 receptor, namely Act1/TRAF6/NF-kB and Act1/TRAF6/p38MAPK signaling by inhibitors, in order to explore the effect of NCR-ILC3 on airway epithelial cells and its potential mechanism in the microenvironment with both cells coexisting. The present study will provide further understanding on mucosal and innate immune responses of lung in COPD, which may contribute to inhibit immune damage of lung.