Gao Jie, Zhang Hongliang, Yang Yanyan, Tao Jinhui
Department of Rheumatology and Immunology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, People's Republic of China.
College of Medicine and Health, Lishui University, Liandu District, No. 1 Xueyuan Road, Lishui, 323000, China.
Inflammation. 2023 Jun;46(3):835-852. doi: 10.1007/s10753-023-01795-5. Epub 2023 Mar 10.
NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a cytoplasmic multiprotein complex composed of the innate immune receptor protein NLRP3, the adapter protein apoptosis-associate speck-like protein containing a caspase recruitment domain (ASC), and the inflammatory protease cysteine-1. Pathogen-associated molecular patterns (PAMPs) or other endogenous danger-associated molecular patterns (DAMPs) activate the NLRP3 inflammasome. As part of the innate immune response, activated NLRP3 promotes GSDMD-dependent pyroptosis, and IL-1β and IL-18 are released during inflammation. Aberrantly activated NLRP3 is deeply involved in various inflammatory diseases. Due to its interaction with adaptive immunity. NLRP3 inflammation has increasingly received attention in autoimmune diseases. Rheumatoid arthritis (RA) is a classic autoimmune disease, which mainly causes bone and cartilage damage. Elevated levels of NLRP3 can be detected in the synovium of RA patients. NLRP3 overactivation is strongly associated with RA activity. Mouse models of spontaneous arthritis has shown that NLRP3/IL-1β axis is implicated in periarticular inflammation in RA. In this review, we describe the current understanding of NLRP3 activation in RA pathogenesis and dissect its impact on innate and adaptive immunity. We also discuss the potential application of specific inhibitors of NLRP3 to provide new therapeutic strategies for treating RA.
NOD样受体家族含pyrin结构域3（NLRP3）炎性小体是一种细胞质多蛋白复合物，由天然免疫受体蛋白NLRP3、衔接蛋白含半胱天冬酶募集结构域的凋亡相关斑点样蛋白（ASC）和炎性蛋白酶半胱氨酸蛋白酶-1组成。病原体相关分子模式（PAMPs）或其他内源性危险相关分子模式（DAMPs）激活NLRP3炎性小体。作为天然免疫反应的一部分，活化的NLRP3促进gasdermin D（GSDMD）依赖性细胞焦亡，炎症期间释放白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）。异常激活的NLRP3深度参与各种炎症性疾病。由于其与适应性免疫的相互作用，NLRP3炎症在自身免疫性疾病中越来越受到关注。类风湿关节炎（RA）是一种典型的自身免疫性疾病，主要导致骨和软骨损伤。在RA患者的滑膜中可检测到NLRP3水平升高。NLRP3过度激活与RA活动密切相关。自发性关节炎小鼠模型表明，NLRP3/IL-1β轴与RA的关节周围炎症有关。在这篇综述中，我们描述了目前对RA发病机制中NLRP3激活的理解，并剖析了其对天然免疫和适应性免疫的影响。我们还讨论了NLRP3特异性抑制剂的潜在应用，为治疗RA提供新的治疗策略。
