IP-10介导Teff/Treg失衡在H7N9病毒致急性肺损伤中的作用机制研究

H7N9禽流感病情凶险，病死率高，其主要临床特征为急性肺损伤导致的重症肺炎。我们前期研究发现：干扰素诱导蛋白10（IP-10）表达水平与病程严重程度显著相关，可直接预测疾病的进展和预后，且病理组织提示H7N9患者肺部出现大量T细胞聚集，目前已知效应T细胞（Teff）和调节性T细胞（Treg）比例失衡在靶器官损伤中发挥了重要作用，且IP-10可参与趋化Teff与Treg。因此本研究推测IP-10通过介导Teff和Treg平衡失调参与急性肺损伤的发生发展。本项目拟通过构建IP-10基因干扰及过表达肺泡上皮细胞株并感染H7N9病毒，明确IP-10表达水平变化与细胞损伤程度的量效关系。并经H7N9病毒感染野生型及IP-10基因敲除小鼠构建急性肺损伤模型，进一步分析IP-10通过介导Teff/Treg失衡导致急性肺损伤的确切作用机制，为H7N9禽流感治疗提供新思路。

H7N9 avian influenza is a dangerous disease with high mortality. Its main characteristic is severe pneumonia caused by acute lung injury. Our previous study found that expression level of interferon induced protein 10 (IP-10) was significantly associated with severity of disease and was able to predict progression and prognosis of the disease directly. Pathologic tissue showed a large number of T cells accumulated in the lungs of patients with H7N9. It is currently known that effector T cell (Teff) and regulatory T cell (Treg) imbalance plays an important role in organ injury and IP-10 may be involved in chemotaxis of Teff and Treg. Therefore, in this study, we assume that IP-10 is involved in the development of acute lung injury by mediating Teff and Treg imbalance. We aim to clarify the dose-effect relationship between IP-10 expression and cell injury degree by constructing alveolar epithelial cell line with IP-10 gene interference and overexpression and infecting H7N9 virus. We would also infect wild type and IP-10 gene knockout mice with H7N9 in order to construct acute lung injury model, and analyze the exact mechanism of acute lung injury caused by IP-10-mediated Teff and Treg imbalance, providing novel ways for treatment of H7N9 avian influenza.