Colciaghi Francesca, Costanza Massimo
Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Front Immunol. 2022 Jul 1;13:915392. doi: 10.3389/fimmu.2022.915392. eCollection 2022.
Over the past nearly two decades, increasing evidence has uncovered how immune cells can actively extrude genetic material to entrap invading pathogens or convey sterile inflammatory signals that contribute to shaping immune responses. Originally identified in neutrophils, the release of decondensed chromatin fibers decorated with antimicrobial proteins, called extracellular traps (ETs), has been recognized as a specific form of programmed inflammatory cell death, which is now known to occur in several other leukocytes. Subsequent reports have shown that self-DNA can be extruded from immune cells even in the absence of cell death phenomena. More recent data suggest that ETs formation could exacerbate neuroinflammation in several disorders of the central nervous system (CNS). This review article provides an overview of the varied types, sources, and potential functions of extracellular DNA released by immune cells. Key evidence suggesting the involvement of ETs in neurodegenerative, traumatic, autoimmune, and oncological disorders of the CNS will be discussed, outlining ongoing challenges and drawing potentially novel lines of investigation.
在过去近二十年里,越来越多的证据揭示了免疫细胞如何能够主动排出遗传物质,以捕获入侵的病原体或传递无菌性炎症信号,这些信号有助于塑造免疫反应。最初在中性粒细胞中发现的,装饰有抗菌蛋白的解聚染色质纤维的释放,称为细胞外陷阱(ETs),已被认为是一种程序性炎症细胞死亡的特殊形式,现在已知在其他几种白细胞中也会发生。随后的报告表明,即使在没有细胞死亡现象的情况下,自身DNA也可以从免疫细胞中排出。最近的数据表明,ETs的形成可能会加剧中枢神经系统(CNS)几种疾病中的神经炎症。这篇综述文章概述了免疫细胞释放的细胞外DNA的不同类型、来源和潜在功能。将讨论表明ETs参与中枢神经系统神经退行性、创伤性、自身免疫性和肿瘤性疾病的关键证据,概述当前面临的挑战并提出潜在的新研究方向。