Fig. 5

NETs in diseases. NETs are involved in various human diseases. NETs are central to the immune response against infectious agents, yet their role can be linked to a double-edged sword due to their potential to exacerbate tissue damage under conditions of sustained inflammation or persistent stimuli. NETs are implicated in a spectrum of nonpathogenic diseases, including sterile inflammation, autoimmune disorders, metabolic dysregulation, thrombosis, pregnancy-related diseases, and tumors, when dysregulated. Under sterile conditions, various stimuli, such as IL-8, immune complexes, and crystals, can facilitate the formation of NETs, leading to conditions like gouty arthritis. AggNETs facilitate the resolution of sterile inflammation. NETs are also implicated in pancreatitis and I/R injuries such as brain and liver I/R. In autoimmune disorders, beyond their pro-inflammatory function, NETs have emerged as potential autoantigens, contributing to the production of autoantibodies. NETs contribute to the disease process of T1D, while further investigation is required for their involvement in T2D. Circulating NET markers positively correlate with glycated HbA1c levels and the severity of diabetic complications. Additionally, NETs promote the progression of MASLD, from steatosis to MASH-HCC. NETs are also implicated in both venous (DVT and pulmonary embolism) and arterial thrombotic events (atherosclerosis, coronary artery disease, and ischemic stroke). Furthermore, NETs are associated with several pregnancy-related diseases, such as pre-eclampsia, spontaneous abortions, and gestational diabetes, contributing to their pathogenesis. The protumorigenic role of NETs in various cancers has been confirmed, although a bidirectional interplay between cancer cells and NETs is proposed. This figure was created by Adobe Illustrator Artwork 16.0 (Adobe Systems, USA)