Department of Microbiology, University of Chicago, Chicago, IL, USA.
Immunology. 2021 Mar;162(3):262-267. doi: 10.1111/imm.13290. Epub 2020 Dec 20.
The nucleotide-binding domain leucine-rich repeat containing receptors (NLRs) are a family of evolutionarily conserved proteins. Several members of NLRs, notably NLRP1, NLRP3 and NLRC4, are able to form cytosolic oligomeric signalling platforms termed inflammasomes to mediate immune response towards pathogens, damage and stress. However, the functions of many NLRs still remain elusive. In the past few years, a couple of less-characterized NLR members are emerging as important signalling molecules with fundamental functions in host defence and inflammation. Among them, NLRP9 is an NLR originally proposed to be expressed and function solely in the reproductive system. Recent evidence has suggested that NLRP9 is also capable of initiating inflammasome formation in the intestine to restrict replication and damage brought by rotavirus infection. Here, we highlight the latest progress in characterization of the role of NLRP9 in infectious and inflammatory diseases, as well as the newest crystallographic and biochemical studies on NLRP9. Finally, we discuss some important questions remained to be answered regarding the molecular and cellular mechanisms governing NLRP9's function in innate immunity and inflammation.
核苷酸结合域富含亮氨酸重复受体（NLRs）是一组进化上保守的蛋白质。NLRs 的几个成员，特别是 NLRP1、NLRP3 和 NLRC4，能够形成细胞溶质寡聚信号平台，称为炎性体，以介导针对病原体、损伤和应激的免疫反应。然而，许多 NLRs 的功能仍然难以捉摸。在过去的几年中，一些研究较少的 NLR 成员作为重要的信号分子出现，它们在宿主防御和炎症中具有基本功能。其中，NLRP9 是一种最初被提出仅在生殖系统中表达和发挥功能的 NLR。最近的证据表明，NLRP9 也能够在肠道中启动炎性体形成，以限制轮状病毒感染带来的复制和损伤。在这里，我们强调了 NLRP9 在感染和炎症性疾病中的作用的最新特征，以及 NLRP9 的最新晶体学和生化研究。最后，我们讨论了一些关于 NLRP9 在先天免疫和炎症中功能的分子和细胞机制的重要问题。
