A4GNT参与TFF2抑制急性呼吸道炎症反应的分子机制

急性呼吸道感染引发的疫情频发，其共性临床特征是免疫失衡导致的异常炎症反应，严重者引发急性呼吸道窘迫综合症乃至预后不佳。呼吸道局部而非系统性的炎症干预策略，可降低全身使用糖皮质激素等药物带来的副作用，有效改善患者临床转归。我们在前期研究中发现，呼吸道局部给予宿主分泌肽TFF2可抑制炎症反应，改善急性呼吸道感染的预后。然而，TFF2抑制炎症反应的机制不清楚，我们通过体外细胞模型发现A4GNT是TFF2与靶细胞结合的关键分子，而EGFR可能是TFF2的一个候选受体。本课题拟在此基础上，首先采用体外细胞模型，通过免疫共沉淀等技术，进一步鉴定TFF2与A4GNT、候选受体（EGFR）的作用方式，阐明TFF2通过A4GNT抑制靶细胞炎症反应的分子机制，随后在体内进一步验证A4GNT的功能。预期研究结果将有助于深入理解TFF2抑制炎症的作用机理，为TFF2干预急性呼吸道感染的临床应用提供理论基础。

The epidemics caused by acute respiratory infections occur frequently, and their common clinical features include abnormal inflammatory responses caused by immune imbalance, and even ARDS or poor prognosis. Local rather than systemic airway inflammation intervention strategy may reduce the side effects of systemic use of glucocorticoids or other drugs, so as to effectively improve the clinical prognosis of patients. In previous studies, we found that local administration of TFF2 to the respiratory tract inhibited inflammatory responses and improved the prognosis of hosts infected by acute respiratory virus. However, the mechanism of TFF2 inhibiting inflammation remains unknown. By in vitro cell models, we identify for the first time that A4GNT is a key molecule for TFF2 binding to target cells, and EGFR may be a candidate receptor for TFF2. Based on this, we firstly use the immunoprecipitation technique by in vitro cell model to further elucidate how TFF2 interact with A4GNT and a candidate receptor (EGFR), and clarify the molecular mechanism how TFF2 inhibit the inflammatory response of target cells through A4GNT, then, the anti-inflammatory function of A4GNT was further verified in vivo. This project will reveal the molecular mechanism of TFF2 mediated inhibition of inflammation, and provide a theoretical basis for the clinical application of TFF2 in the prevention and treatment of acute respiratory infection.