Scalavino Viviana, Piccinno Emanuele, Giannelli Gianluigi, Serino Grazia
National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy.
Int J Mol Sci. 2024 Dec 4;25(23):13058. doi: 10.3390/ijms252313058.
NOD-like receptors (NLRs) are a family of cytosolic pattern recognition receptors (PRRs) implicated in the innate immune sensing of pathogens and damage signals. NLRs act as sensors in multi-protein complexes called inflammasomes. Inflammasome activity is necessary for the maintenance of intestinal homeostasis, although their aberrant activation contributes to the pathogenesis of several gastrointestinal diseases. In this review, we summarize the main features of the predominant types of inflammasomes involved in gastrointestinal immune responses and their implications in intestinal disease, including Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (IBD), celiac disease, and Colorectal Cancer (CRC). In addition, we report therapeutic discoveries that target the inflammasome pathway, highlighting promising novel therapeutic strategies in the treatment of intestinal diseases. Collectively, our understanding of the mechanisms of intestinal inflammasome activation and their interactions with other immune pathways appear to be not fully elucidated. Moreover, the clinical relevance of the efficacy of inflammasome inhibitors has not been evaluated. Despite these limitations, a greater understanding of the effectiveness, specificity, and reliability of pharmacological and natural inhibitors that target inflammasome components could be an opportunity to develop new therapeutic options for the treatment of intestinal disease.
NOD样受体（NLRs）是一类胞质模式识别受体（PRRs），参与病原体和损伤信号的固有免疫感知。NLRs在称为炎性小体的多蛋白复合物中充当传感器。炎性小体活性对于维持肠道稳态是必需的，尽管它们的异常激活会导致几种胃肠道疾病的发病机制。在这篇综述中，我们总结了参与胃肠道免疫反应的主要类型炎性小体的主要特征及其在肠道疾病中的意义，包括肠易激综合征（IBS）、炎症性肠病（IBD）、乳糜泻和结直肠癌（CRC）。此外，我们报告了针对炎性小体途径的治疗发现，强调了在肠道疾病治疗中有前景的新治疗策略。总体而言，我们对肠道炎性小体激活机制及其与其他免疫途径相互作用的理解似乎尚未完全阐明。此外，炎性小体抑制剂疗效的临床相关性尚未得到评估。尽管有这些局限性，但对靶向炎性小体成分的药理和天然抑制剂的有效性、特异性和可靠性有更深入的了解，可能是开发肠道疾病新治疗选择的一个机会。
