Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Front Immunol. 2024 Aug 7;15:1425251. doi: 10.3389/fimmu.2024.1425251. eCollection 2024.
Ulcerative colitis (UC) is characterized by chronic non-recessive inflammation of the intestinal mucosa involving both innate and adaptive immune responses. Currently, new targeted therapies are urgently needed for UC, and neutrophil extracellular traps (NETs) are new therapeutic options. NETs are DNA-based networks released from neutrophils into the extracellular space after stimulation, in which a variety of granule proteins, proteolytic enzymes, antibacterial peptides, histones, and other network structures are embedded. With the deepening of the studies on NETs, their regulatory role in the development of autoimmune and autoinflammatory diseases has received extensive attention in recent years. Increasing evidence indicates that excess NETs exacerbate the inflammatory response in UC, disrupting the structure and function of the intestinal mucosal barrier and increasing the risk of thrombosis. Although NETs are usually assigned a deleterious role in promoting the pathological process of UC, they also appear to have a protective role in some models. Despite such progress, comprehensive reviews describing the therapeutic promise of NETs in UC remain limited. In this review, we discuss the latest evidence for the formation and degradation of NETs, focusing on their double-edged role in UC. Finally, the potential implications of NETs as therapeutic targets for UC will be discussed. This review aims to provide novel insights into the pathogenesis and therapeutic options for UC.
溃疡性结肠炎(UC)的特征是肠黏膜的慢性非隐性炎症,涉及固有和适应性免疫反应。目前,UC 迫切需要新的靶向治疗方法,而中性粒细胞胞外诱捕网(NETs)是新的治疗选择。NETs 是中性粒细胞在受到刺激后释放到细胞外空间的基于 DNA 的网络,其中嵌入了多种颗粒蛋白、蛋白水解酶、抗菌肽、组蛋白和其他网络结构。随着对 NETs 研究的深入,近年来其在自身免疫和自身炎症性疾病发展中的调节作用受到了广泛关注。越来越多的证据表明,过量的 NETs 会加重 UC 中的炎症反应,破坏肠道黏膜屏障的结构和功能,并增加血栓形成的风险。尽管 NETs 在促进 UC 的病理过程中通常被认为是有害的,但它们在某些模型中似乎也具有保护作用。尽管取得了这些进展,但描述 NETs 在 UC 中治疗潜力的全面综述仍然有限。在这篇综述中,我们讨论了 NETs 的形成和降解的最新证据,重点介绍了它们在 UC 中的双刃剑作用。最后,还将讨论 NETs 作为 UC 治疗靶点的潜在意义。本综述旨在为 UC 的发病机制和治疗选择提供新的见解。