NLRP3作为最重要的NLR家族成员，能够识别多种外来病原体相关分子模式（PAMP）和自身产生的危险信号（DAMP），进而与接头蛋白ASC以及pro-caspase1形成称为"炎症小体"的蛋白复合物，切割pro-IL-1和pro-IL-18形成成熟形式。炎症小体促进机体抵抗外来病原体，而过度反应又会损伤机体导致各种疾病。因此，NLRP3功能的活化和精细调控机制是一个有待深入研究的前沿科学问题。我们发现新分子核苷酸去磷酸化酶MNE4和一氧化氮NO分别从正反两个方向调控NLRP3炎症小体的活化。通过体外重构系统，细胞模型和动物模型，证明了它们对炎症小体的调控作用。我们将深入研究其作用靶点和机制，在已构建好的基因敲除小鼠体内，进一步验证其功能。本课题是一项原始创新研究工作，通过研究NLRP3炎症小体所调控的细胞机制，可以为炎症相关疾病如败血症，关节炎等的新药开发提供新的思路，具有重要的科学意义。

As a most important NLR member, NLRP3 recognize a diverse set of inflammation-inducing stimuli that include PAMPs and DAMPs and control the production of important pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-18. NLRP3 inflammasome is essential for eliciting immune response to pathogens. However, excessive activation contributes to the tissue pathogenesis. Therefore, it must be under tight control. Mechanisms of the NLRP3 inflammasome activation and regulation have been the forefront scientific research realm. Here we found NME4 and a small molecule with multiple bioactivity - NO, could positively and negatively regulate NLRP3 inflammasome activation respectively. In vitro reconstruction system and in vivo assays all suggested there function in regulating NLRP3 inflammasome activation. Now we have constructed the gene knockout mice and we will further go into their targets and function mechanisms and also prove their functions in vivo using animal inflammation model. Our investigation is an original innovation research which will be helpful in developing new therapeutic target to inflammation disease such as endotoxic shock and arthritis.