NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) is a cytosolic innate immune sensor of cellular stress signals, triggered by infection and sterile inflammation. Upon detection of an activating stimulus, NLRP3 transitions from an inactive homo-oligomeric multimer into an active multimeric inflammasome, which promotes the helical oligomeric assembly of the adaptor molecule ASC. ASC oligomers provide a platform for caspase-1 activation, leading to the proteolytic cleavage and activation of proinflammatory cytokines in the IL-1 family and gasdermin D, which can induce a lytic form of cell death. Recent studies investigating both the cellular requirement for NLRP3 activation and the structure of NLRP3 have revealed the complex regulation of NLRP3 and the multiple steps involved in its activation. This review presents a perspective on the biochemical and cellular processes controlling the assembly of the NLRP3 inflammasome with particular emphasis on structural regulation and the role of organelles. We also highlight the latest research on metabolic control of this inflammatory pathway and discuss promising clinical targets for intervention.

NOD-、LRR- 和含有 pyrin 结构域的 3 (NLRP3) 是细胞应激信号的细胞溶质先天免疫传感器，由感染和无菌炎症触发。在检测到激活刺激后，NLRP3 从无活性的同源寡聚多聚体转变为活性多聚体炎性体，从而促进衔接分子 ASC 的螺旋寡聚组装。ASC 寡聚体为 caspase-1 激活提供了一个平台，导致 IL-1 家族和 gasdermin D 中促炎细胞因子的蛋白水解切割和激活，这可以诱导裂解形式的细胞死亡。最近调查 NLRP3 激活的细胞需求和 NLRP3 结构的研究揭示了 NLRP3 的复杂调节及其激活所涉及的多个步骤。这篇综述提出了控制 NLRP3 炎性体组装的生化和细胞过程的观点，特别强调结构调节和细胞器的作用。我们还重点介绍了该炎症通路代谢控制的最新研究，并讨论了有希望的临床干预目标。