Neutrophil Extracellular Traps in Skin Diseases

Neutrophils are the primary innate immune cells, and serve as sentinels for invading pathogens. To this end, neutrophils exert their effector functions via phagocytosis, degranulation, reactive oxygen species generation, and neutrophil extracellular trap (NET) release. Pathogens and pathogen-derived components trigger NET formation, leading to the clearance of pathogens. However, NET formation is also induced by non-related pathogen proteins, such as cytokines and immune complexes. In this regard, NET formation can be induced under both non-sterile and sterile conditions. NETs are enriched by components with potent cytotoxic and inflammatory properties, thereby occasionally damaging tissues and cells and dysregulating immune homeostasis. Research has uncovered the involvement of NETs in the pathogenesis of several connective tissue diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and ANCA-associated vasculitis. In dermatology, several skin diseases clinically develop local or systemic sterile pustules and abscesses. The involvement of neutrophils and subsequent NET formation has recently been elucidated in these skin diseases. Therefore, this review highlights the NETs in these neutrophil-associated diseases.