II型固有淋巴细胞通过JAK/STAT信号通路介导支气管哮喘气道炎症的机制

哮喘是多种细胞和细胞组分参与的气道炎症性疾病，其经典机制为Th2细胞介导的适应性免疫，近年研究发现II型固有淋巴细胞(ILC2)介导的固有免疫反应也参与哮喘气道炎症且起重要作用。申请者前期研究发现哮喘患者血ILC2显著高于健康对照组，而治疗后ILC2下降与哮喘控制、肺功能改善呈正相关；最新研究进一步发现IL25、IL33和IL2促进患者ILC2中Th2型细胞因子IL5、IL13的表达，该过程与JAK/STAT通路中STAT3磷酸化相关，提示该通路参与ILC2介导的哮喘气道炎症。因此，申请者提出“ILC2通过JAK/STAT信号通路介导哮喘气道炎症”的假设。本研究拟采用流式分选、蛋白印迹和PCR等技术，从临床、动物模型和细胞层面探索并确证ILC2通过激活JAK/STAT信号通路，上调Th2型细胞因子而影响哮喘气道炎症。该项目旨在揭示ILC2参与哮喘炎症具体机制，为哮喘治疗新靶点提供理论依据。

Asthma is chronic airway inflammation characterized with involvement of various cells and cytokines. The classic way of Th2 cells modulating adaptive immunity was believed to play a predominant role in asthmatic airway inflammation. However, new studies found that group 2 innate lymphoid cells (ILC2) also plays an important part in airway inflammation of asthma. Our previous studies found that ILC2 levels increase in peripheral blood in uncontrolled asthma patients, while ILC2 and IL13 levels decrease dramatically after effective therapy and correlated positively to asthmatic control and improvement of pulmonary function. Moreover, our latest analysis revealed that IL5 and IL13 levels in human ILC2s were significantly increased with the stimulation of IL-25, IL-33 plus IL-2, which indicated the involvement of STAT3 in JAK/STAT signal pathway. And these results suggests that JAK/STAT signal pathway involves in ILC2 induced asthmatic airway inflammation. Accordingly, we propose a hypothesis that ILC2 modulates airway inflammation via JAK/STAT signal pathway. In this project, we aim to investigate and confirm that ILC2 up-regulating Th2 related cytokines influences asthmatic airway inflammation via JAK/STAT signaling pathway from clinical patients, animal models and cells by flow cytometry, Western Blot and PCR. We hope to find out the new mechanism of asthmatic airway inflammation, and provide theoretical basis for new therapy target in treating asthma.