Unraveling the priming phase of NLRP3 inflammasome activation: Molecular insights and clinical relevance
Yonghong Liao, Yao Kong, Hongyu Chen, Jing Xia, Jianjun Zhao, Yang Zhou
Abstract
• Priming involves the rapid activation via NLRP3 PTMs in the early phase and transcriptional upregulation in the late phase. • NLRP3 translocates from the ER to the MAMs, dTGN and MTOC sequentially, where it assembles the inflammasome. • Modulating priming presents a promising therapeutic strategy for treating inflammatory diseases. The NLRP3 inflammasome plays a pivotal role in the innate immune response. Its activation involves a two-step mechanism that consists of priming and activation. The priming of the NLRP3 inflammasome is a vital initial phase necessary for its activation and subsequent involvement in the immune response, though its understanding varies across studies. Recent research has identified key proteins that influence the priming process, revealing a sophisticated regulatory network. This review provides a comprehensive review of the priming phase of NLRP3 inflammasome activation, with a particular focus on the underlying molecular mechanisms, including transcriptional regulation, orchestration of the phosphorylation status, deubiquitination and the relationships with the inflammation-associated diseases. Understanding the intricacies of NLRP3 inflammasome priming not only elucidates fundamental aspects of immune regulation, but also provides potential avenues for therapeutic intervention in inflammatory diseases.