成人斯蒂尔病（AOSD）是一种炎症小体激活所介导的免疫炎症性疾病。我们以往的研究揭示AOSD存在I型干扰素通路和NLRC4/NLRP3炎症小体异常活化，而且基因测序发现AOSD患者I型干扰素诱导的炎症调控相关蛋白FOXO3非编码区关键位点基因多态性存在分布差异。另外体外实验揭示I型干扰素可以明显增加携带该突变基因的巨噬细胞IL-1β和IL-18表达。因此，我们提出I型干扰素通过下调FOXO3的表达从而使NLRC4/NLRP3炎症小体激活，最终促进炎症风暴的形成。本研究拟通过患者外周血、细胞系及动物三个层面，首先探索I型干扰素通过下调FOXO3触发AOSD巨噬细胞炎症小体的激活，并进一步揭示FOXO3的下调导致巨噬细胞NLRC4/NLRP3炎症小体激活的具体机制。本研究有望为I型干扰素触发AOSD炎症风暴新的发病机制提供实验依据，并为阐明AOSD潜在的治疗靶点提供理论基础。

Adult-onset Still's disease (AOSD) is an inflammatory disease characterized by inflammasome activation. Our previous studies revealed that type I IFN pathway and NLRC4/NLRP3 inflammasome were activated in AOSD, and a significant difference in the distribution of non-coding region of FOXO3 was found in AOSD by gene sequencing, which is an inflammation regulatory protein induced by type I IFN. In addition, in vitro experiments revealed that type I IFN could significantly increase the expression of IL-1β and IL-18 in macrophages carrying mutant allele. Therefore, we propose that type I IFN can activate NLRC4/NLRP3 inflammasome by inhibiting FOXO3 expression, and finally promote cytokine storm formation. This study intends to explore the mechanism of how type I IFN triggers the activation of macrophage to induce cytokine storm by down regulating FOXO3 in AOSD. We investigate it by patients' peripheral blood, cell lines and animals, and further reveal that down-regulated FOXO3 leads to NLRC4/NLRP3 inflammasome activation in macrophages, and promotes the formation of cytokine storm. This study aims to provide experimental basis to elucidate new pathogenesis of cytokine storm triggered by type I IFN in AOSD, and provide theoretical basis to investigate potential therapeutic targets of AOSD.