Zmora N, Levy M, Pevsner-Fishcer M, Elinav E
Immunology Department, Weizmann Institute of Science, Rehovot, Israel.
Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Mucosal Immunol. 2017 Jul;10(4):865-883. doi: 10.1038/mi.2017.19. Epub 2017 Apr 12.
The inflammasome is a cytosolic multi-protein innate immune rheostat, sensing a variety of endogenous and environmental stimuli, and regulating homeostasis or damage control. In the gastrointestinal tract, inflammasomes orchestrate immune tolerance to microbial and potentially food-related signals or drive the initiation of inflammatory responses to invading pathogens. When inadequately regulated, intestinal inflammasome activation leads to a perpetuated inflammatory response leading to immune pathology and tissue damage. In this review, we present the main features of the predominant types of inflammasomes participating in intestinal homeostasis and inflammation. We then discuss current controversies and open questions related to their functions and implications in disease, highlighting how pathological inflammasome over-activation or impaired function impact gut homeostasis, the microbiome ecosystem, and the propensity to develop gut-associated diseases. Collectively, understanding of the molecular basis of intestinal inflammasome signaling may be translated into clinical manipulation of this fundamental pathway as a potential immune modulatory therapeutic intervention.
炎性小体是一种胞质内的多蛋白固有免疫调节器，可感知多种内源性和环境刺激，并调节体内平衡或损伤控制。在胃肠道中，炎性小体协调对微生物及潜在食物相关信号的免疫耐受，或驱动对入侵病原体的炎症反应启动。当调节不当时，肠道炎性小体激活会导致持续的炎症反应，进而引发免疫病理和组织损伤。在本综述中，我们介绍了参与肠道稳态和炎症的主要类型炎性小体的主要特征。然后，我们讨论了与它们在疾病中的功能和影响相关的当前争议和未解决问题，强调病理性炎性小体过度激活或功能受损如何影响肠道稳态、微生物群落生态系统以及发生肠道相关疾病的倾向。总体而言，对肠道炎性小体信号传导分子基础的理解可能会转化为对这一基本途径的临床操控，作为一种潜在的免疫调节治疗干预手段。
