Department of Medicine, Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Oral and Craniofacial Biomedicine Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nat Rev Immunol. 2019 Aug;19(8):477-489. doi: 10.1038/s41577-019-0165-0.
NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent release of the pro-inflammatory cytokines IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical bases of NLRP3 activation and regulation and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.
NLRP3（核苷酸结合寡聚化结构域样受体家族含pyrin 结构域蛋白 3）是一种细胞内传感器，可识别广泛的微生物基序、内源性危险信号和环境刺激物，从而形成并激活 NLRP3 炎性体。NLRP3 炎性体的组装导致半胱天冬酶 1 依赖性释放促炎细胞因子 IL-1β 和 IL-18，以及天冬氨酸特异性半胱氨酸蛋白酶 1（caspase-1）依赖性的细胞焦亡。最近的研究揭示了 NLRP3 炎性体的新调节因子，包括新的相互作用或调节蛋白、代谢途径和调节线粒体枢纽。在这篇综述中，我们介绍了 NLRP3 激活和调节的分子、细胞生物学和生物化学基础，并描述了这种机制理解如何导致针对 NLRP3 炎性体的潜在治疗方法。
