Th17/Treg失衡是介导非嗜酸性粒细胞性哮喘（NEA）的关键，但内在调控机制尚不清楚。我们前期研究发现，NEA小鼠气道内ATP聚集，并激活肺泡巨噬细胞(AM) NLRP3炎性小体，产生正向调控Th17分化的IL-1β，促进Th17极化；而ATP水解酶CD39在AM上表达明显下调，进一步阻断小鼠体内CD39，则加重气道内ATP聚集以及Th17极化。据此假设，AM通过下调CD39，导致气道内ATP聚集，激活NLRP3炎性小体，促进Th17/Treg失衡。故本课题拟明确NEA小鼠肺泡巨噬细胞CD39/ATP轴与NLRP3炎性小体表达、Th17/Treg失衡的关联；体外AM及Th0共培养探讨CD39/ATP轴调控Th17分化的作用机制；体内AM过继并干预CD39/ATP轴，最终阐明NLRP3炎性小体介导肺泡巨噬细胞CD39/ATP轴调控Th17/Treg极化失衡的机制，为防治NEA提供新思路。

The imbalance of Th17/Treg polarization is a key pathogenesis to non-eosinophilic asthma (NEA), but its regulatory mechanism is still unclear.Our previous study showed that ATP accumulated in the airway of NEA model mouse，activated NLRP3 inflammasome in alveolar macrophages (AM), and produced IL-1β,which promotes the differentiation and polarization of Th17 cell; while the expression of CD39, which can hydrolyze extracellular ATP, was significantly reduced on AM. Further, blocking CD39 expression on AM led to the ATP accumulation in airway and Th17 polarization. Accordingly, we assume that the down-regulation of CD39 expression on AM leads to ATP accumulation in airway, and activates NLRP3 inflammasome in AM, and results in the diseqilibrium of Th17 / Treg polarization. Therefore, this study intends to validate that CD39/ATP axis has a regulatory role in NLRP3 inflammasome activation and Th17/Treg polarization in NEA model mouse; The co-culture experiments of AM and Th0 cells will explore the effects of CD39/ATP axis on regulating Th17 differentiation in vitro; By using the adoptive AM and the interventions in CD39/ATP axis, we ultimately clarify the mechanism of NLRP3 inflammasome-mediated CD39/ATP axis in regulating Th17/Treg polarization of NAE, and provide a new thought in preventing and combating NEA.