Gasdermin-D是新近发现的炎性小体诱导IL-1β释放和细胞焦亡的关键分子，其活性调控机制尚未明确。课题组发现LAPF在巨噬细胞特异性缺陷后，IL-1β释放和细胞焦亡减少；肠上皮特异性缺陷LAPF小鼠DSS诱导的结肠炎损伤更少； LAPF可以结合并与GSDMD共定位。提示LAPF可能结合GSDMD促进活化、并促进细胞焦亡、加重感染或非感染引起的炎症损伤。课题组拟进一步应用LAPF在肠上皮或巨噬细胞特异性缺陷的小鼠模型、应用体内动物疾病模型研究LAPF促进GSDMD诱导细胞焦亡在感染性与非感染性炎症反应中的体内效应；应用分离培养原代细胞体外模型、信号转导和相互作用分析，研究LAPF通过细胞膜结合PIP成分，促进GSDMD在细胞膜定位、聚集与活化的现象促进细胞焦亡的细胞学与分子生物学效应。课题将为发现GSDMD诱导的细胞焦亡在感染性与非感染性炎症中生理与病理意义提供理论基础和药物靶点。

Inflammasome induces the cleavage of IL-1β by sensing the intracellular pathogen motif or extracellular dangerous signal, in which Gasdermin-D plays a critical function by regulating IL-1β exocytosis and inducing pyroptosis. However, the activation and regulation mechanism of GSDMD remains to be elusive. We found that macrophage-specific deficiency of LAPF decreased IL-β production and cell pyroptosis， intestine-specific deficiency of LAPF protected DSS-induced colitis， LAPF interacted and co-localized with GSDMD. Above data indicated that LAPF may aggravate infectious or non-infectious inflammation by promoting GSDMD activation and cell pyroptosis. The proposal plans to explore the in vivo function of LAPF in infectious or non-infectious inflammation by promoting GSDMD activation and cell pyroptosis, explore the in vitro function of LAPF by binding PIP and promoting the localization to membrane and assemble of GSDMS and increasing cell pyroptosis at cellular and molecular level. The accomplishment of the proposal will provide novel theory evidence for physiological and pathological function of GSDMD and pyroptosis and also new light on regulation mechanism and drug targets for the infectious or non-infectious inflammation and the related diseases.