玉屏风散调控ILC2细胞的记忆及体内迁移从而干预过敏性哮喘复发的机制研究

益气固表方玉屏风散（YPFS）广泛用于过敏性哮喘，优势在于缓解期应用减少复发。课题组研究发现YPFS能调控哮喘患者及小鼠模型缓解期存在的记忆样2型固有淋巴细胞（ILC2）数量、功能及其肠-肺迁移。基于此提出假说：“记忆样ILC2细胞是介导上皮屏障持续损伤进而引起过敏性哮喘复发的关键病理因素，玉屏风散中不同成分群通过调控ILC2的记忆和体内迁移过程中的系列靶点，缓解呼吸道上皮屏障持续损伤，减少过敏性哮喘复发”。拟进一步确证记忆样ILC2细胞是YPFS缓解哮喘复发的靶细胞；并验证记忆样ILC2在介导上皮屏障破坏，进而引起哮喘复发中的关键作用，探索其体内迁移机制；在此基础上筛选YPFS调控ILC2记忆及其体内迁移的活性成分群，明确YPFS的系列靶点及作用机制。通过本研究揭示YPFS益气固表治法的科学内涵；产生系列活性化合物，为进一步开发打下基础；并为临床提供缓解期干预哮喘复发的靶细胞和系列靶点。

Yu-ping-feng-san (YPFS), a typical example of tonifying qi and strengthening exterior prescriptions, is broadly used in clinic to treat allergic asthma. Comparing with western medicine, YPFS applied in the remission phase has unique advantages in reducing the risk of recurrence of allergic diseases. Previous experimental work of our group suggested that YPFS was potent to dampen the memory-like and interorgan migration properties of the abundant type 2 innate lymphoid cells (ILC2s) in vivo during remission phase of both allergic asthmatic patients and mice model. Based on it, we hypothesis that: Memory-like ILC2s might be the pivotal cause of bronchial epithelial barrier deficiency, which further lead to the recurrence of allergic asthma; Different components of YPFS might regulate the memory-gaining and interorgan-trafficking properties of ILC2s, respectively, contributing to the restoration of the bronchial epithelial barrier and alleviation of asthma recurrence. We plan to verify our hypothesis by: (1) further determining that YPFS reduces recurrence of allergic asthma by regulating memory-like ILC2s; (2) verifying the critical role of memory-like ILC2s in disturbing bronchial epithelial barrier and then inducing allergic asthma relapse; (3) exploring the dependent signalings of interorgan-trafficking of memory-like ILC2s; (4) illuminating the active ingredients in YPFS and corresponding targets involved in the memory-gaining and interorgan-migrating processes of ILC2. In this way, we could illuminate the functional significance of memory-like property and trafficking capability of ILC2 in the pathology of allergic asthma recurrence, so that it may throw lights on making memory-like ILC2s as the promising target cells to alleviate allergic asthma recurrence. Furthermore, this research is promising in revealing the scientific explanation of tonifying qi and strengthening exterior. Finally, we may provide several active ingredients in ameliorating asthma recurrence, which could promote the development of novel medications against this disease.