Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
Cell Death Differ. 2023 Apr;30(4):861-875. doi: 10.1038/s41418-023-01124-1. Epub 2023 Feb 8.
Extracellular chromatin, for example in the form of neutrophil extracellular traps (NETs), is an important element that propels the pathological progression of a plethora of diseases. DNA drives the interferon system, serves as autoantigen, and forms the extracellular scaffold for proteins of the innate immune system. An insufficient clearance of extruded chromatin after the release of DNA from the nucleus into the extracellular milieu can perform a secret task of moonlighting in immune-inflammatory and occlusive disorders. Here, we discuss (I) the cellular events involved in the extracellular release of chromatin and NET formation, (II) the devastating consequence of a dysregulated NET formation, and (III) the imbalance between NET formation and clearance. We include the role of NET formation in the occlusion of vessels and ducts, in lung disease, in autoimmune diseases, in chronic oral disorders, in cancer, in the formation of adhesions, and in traumatic spinal cord injury. To develop effective therapies, it is of utmost importance to target pathways that cause decondensation of chromatin during exaggerated NET formation and aggregation. Alternatively, therapies that support the clearance of extracellular chromatin are conceivable.
细胞外染色质，例如中性粒细胞细胞外陷阱 (NETs) 的形式，是推动多种疾病病理进展的重要因素。DNA 驱动干扰素系统，作为自身抗原，并为先天免疫系统的蛋白质形成细胞外支架。从细胞核释放到细胞外环境中的 DNA 后，挤出的染色质如果不能被充分清除，可能会在免疫炎症和闭塞性疾病中执行兼职的秘密任务。在这里，我们讨论了（I）染色质细胞外释放和 NET 形成涉及的细胞事件，（II）NET 形成失调的破坏性后果，以及（III）NET 形成和清除之间的失衡。我们包括 NET 形成在血管和管道闭塞、肺部疾病、自身免疫性疾病、慢性口腔疾病、癌症、粘连形成以及创伤性脊髓损伤中的作用。为了开发有效的治疗方法，靶向导致染色质在 NET 形成和聚集过程中解凝聚的途径至关重要。或者，可以设想支持清除细胞外染色质的治疗方法。
