Liu Ying, Deng Heng, Yao Jinfeng, He Chunrong, Zhang Jun
College of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China.
Department of Anorectal Surgery, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.
Heliyon. 2024 Nov 20;10(23):e40577. doi: 10.1016/j.heliyon.2024.e40577. eCollection 2024 Dec 15.
Crohn's disease (CD) is an idiopathic and chronic inflammation of the gastrointestinal (GI) tract. The underlying pathogenesis of CD is multifaceted, with complex interactions between genetic predisposition, environmental triggers, and abnormalities within the immune system. Neutrophil extracellular traps (NETs) have gained significant attention as a novel component in the pathogenesis of CD. NETs are intricate structures fashioned from DNA, histones, and granule proteins, and are actively released by neutrophils to entangle and eliminate pathogenic microbes. This review article delves into the intricate role of NETs in the pathogenesis of CD. We examine how NETs may serve as a pivotal mechanism for the recruitment of immune cells to the site of inflammation. NETs are known to influence the function of epithelial cells, which line the GI tract, potentially contributing to the structural integrity and barrier dysfunction observed in CD. NETs stimulate inflammation, a hallmark of the disease, by releasing pro-inflammatory molecules and activating immune cells. We also investigate the promising therapeutic potential of targeting NETs in CD. By intercepting the formation or function of NETs, it may be possible to mitigate the chronic inflammation, reduce tissue damage, and alleviate the symptoms associated with CD. Strategies to inhibit NET formation, such as the use of DNase I and approaches to disrupt NET-mediated signaling pathways, are discussed in CD therapeutics. Understanding the detailed mechanisms of NETs is crucial for the development of targeted treatments that could potentially revolutionize the management of CD.
克罗恩病（CD）是一种特发性的胃肠道慢性炎症。CD的潜在发病机制是多方面的，涉及遗传易感性、环境触发因素以及免疫系统异常之间的复杂相互作用。中性粒细胞胞外陷阱（NETs）作为CD发病机制中的一种新成分受到了广泛关注。NETs是由DNA、组蛋白和颗粒蛋白构成的复杂结构，由中性粒细胞主动释放以缠结和清除致病微生物。这篇综述文章深入探讨了NETs在CD发病机制中的复杂作用。我们研究了NETs如何作为免疫细胞募集到炎症部位的关键机制。已知NETs会影响胃肠道内衬的上皮细胞功能，这可能导致CD中观察到的结构完整性和屏障功能障碍。NETs通过释放促炎分子和激活免疫细胞来刺激炎症，这是该疾病的一个标志。我们还研究了针对CD中NETs的有前景的治疗潜力。通过阻断NETs的形成或功能，有可能减轻慢性炎症、减少组织损伤并缓解与CD相关的症状。CD治疗中讨论了抑制NET形成的策略，如使用脱氧核糖核酸酶I以及破坏NET介导的信号通路的方法。了解NETs的详细机制对于开发可能彻底改变CD治疗的靶向治疗方法至关重要。
