Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
The Centre of Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China.
Front Immunol. 2019 Feb 28;10:276. doi: 10.3389/fimmu.2019.00276. eCollection 2019.
NLRP3 inflammasome can be widely found in epithelial cells and immune cells. The NOD-like receptors (NLRs) family member NLRP3 contains a central nucleotide-binding and oligomerization (NACHT) domain which facilitates self-oligomerization and has ATPase activity. The C-terminal conserves a leucine-rich repeats (LRRs) domain which can modulate NLRP3 activity and sense endogenous alarmins and microbial ligands. In contrast, the N-terminal pyrin domain (PYD) can account for homotypic interactions with the adaptor protein-ASC of NLRP3 inflammasome. These characters enable it function in innate immunity. Its downstream effector proteins include caspase-1 and IL-1β etc. which exhibit protective or detrimental roles in mucosal immunity in different studies. Here, we comprehensively review the current literature regarding the physiology of NLRP3 inflammasome and its potential roles in the pathogenesis of IBD. We also discuss about the complex interactions among the NLRP3 inflammasome, mucosal immune response, and gut homeostasis as found in experimental models and IBD patients.
NLRP3 炎性体广泛存在于上皮细胞和免疫细胞中。NOD 样受体（NLRs）家族成员 NLRP3 包含一个中央核苷酸结合和寡聚化（NACHT）结构域，该结构域有助于自身寡聚化并具有 ATP 酶活性。C 末端保守有富含亮氨酸重复（LRRs）结构域，该结构域可以调节 NLRP3 活性并感知内源性警报素和微生物配体。相比之下，N 端吡喃结构域（PYD）可以与 NLRP3 炎性体的衔接蛋白 ASC 发生同源相互作用。这些特性使其在先天免疫中发挥作用。其下游效应蛋白包括 caspase-1 和 IL-1β 等，在不同的研究中在黏膜免疫中表现出保护或有害作用。在这里，我们全面回顾了 NLRP3 炎性体的生理学及其在 IBD 发病机制中的潜在作用的当前文献。我们还讨论了 NLRP3 炎性体、黏膜免疫反应和肠道内稳态之间在实验模型和 IBD 患者中发现的复杂相互作用。
