Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, Sydney, New South Wales, Australia.
Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
J Leukoc Biol. 2020 Sep;108(3):925-935. doi: 10.1002/JLB.3MR0720-472RR. Epub 2020 Aug 17.
The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one of the most well-characterized inflammasomes, activated by pathogen-associated molecular patterns and damage-associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut-lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut-lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.
核苷酸结合寡聚化结构域（NOD）样受体（NLR）家族，包含pyrin 结构域的蛋白 3（NLRP3）炎性小体，是最典型的炎性小体之一，由病原体相关分子模式和损伤相关分子模式激活，包括来自共生或致病性细菌和病毒感染。NLRP3 炎性小体促进炎症细胞募集，并调节胃肠道和肺部等组织中的免疫反应，参与影响肠道和肺部的许多疾病。最近，肠道和肺部的微生物组以及这些器官之间的串扰（肠-肺轴）被确定为一种潜在的机制，可能以双向方式影响疾病。在这篇综述中，我们重点介绍了 2019 年炎症世界大会上该领域的主题。我们讨论了最近的证据，说明微生物组如何影响肠道和肺部 NLRP3 炎性小体的反应，该炎性小体在调节肠道和肺部炎症中的作用在疾病中，及其在肠-肺轴中的潜在作用。我们强调了由于 NLRP3 炎性小体抑制剂 MCC950 的合成，我们对 NLRP3 炎性小体的理解呈指数级增长，并提出了可能进一步阐明 NLRP3 炎性小体在肠道和肺部疾病中作用的未来研究。
