难治性鼻窦炎（RCRS）经规范化手术、鼻用/口服糖皮质激素（GC）治疗效果不佳，对GC抵抗是关键因素之一。焦亡相关因子caspase-1过表达促GC抵抗，但机制不明。我们研究发现RCRS鼻黏膜caspase-1、Tc17和IL-17A均高表达，IL-17A活化NF-κB（Front Immunol, 2018），并上调caspase-1表达。据此推测：Tc17/IL-17A调控NF-κB/NLRP3-caspase-1介导细胞焦亡、促进GC抵抗。本研究拟证实RCRS鼻黏膜局部焦亡增加、并与Tc17/IL-17A高表达相关；阐明IL-17A调控NF-κB/NLRP3-caspase-1通路介导鼻黏膜上皮细胞/Th2细胞焦亡，抑GC受体表达、促炎症因子释放的机制；鼻窦炎小鼠验证抑IL-17A可减少细胞焦亡，增强GC疗效。将从细胞焦亡这一新视角揭示RCRS对GC抵抗的机制，为改善预后提供新思路。

Refractory chronic rhinosinusitis (RCRS) does not achieve satisfactory outcomes with adequate surgery and intranasal/oral glucocorticoid (GC). One of the pivotal factors is GC resistance. It has been reported that the overexpression of caspase-1, one of pyroptosis-related factors, promoted GC resistance, but the mechanism is still unclear. Our study found that the expression of caspase-1, Tc17 and IL-17A were all highly expressed in nasal mucosal of RCRS. And IL-17A could active NF-κB（Front Immunol, 2018）and promote the expression of caspase-1. So it is speculated that Tc17/IL-17A promotes GC resistance by inducing cell pyroptosis via activating NF-κB/NLRP3-caspase-1. This study intends to identify the cell pyroptosis in RCRS, which is associated with the high expression of Tc17/IL-17A. Then, we will demonstrate the mechanism that IL-17A induces cell pyroptosis in nasal mucosal epithelium and Th2 cells, and then inhibits the expression of GC receptors to increase the release of inflammatory cytokines in vitro. Finally, CRS mice model will be conducted to confirm that inhibition of IL-17A can reduce cell pyroptosis, and improve therapeutic effect. This study will reveal a new mechanism of GC resistance in RCRS from a new perspective of pyroptosis, and provide new ideas for improving prognosis of RCRS.