Neutrophils and neutrophil extracellular traps in the liver and gastrointestinal system

• Published in: Nature reviews. Gastroenterology & hepatology Vol. 15; no. 4; pp. 206 - 221
• Main Authors: Honda, Masaki, Kubes, Paul
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2018; Nature Publishing Group
• Subjects: 631/250/2504/223/1699; 692/4020/2741; 692/4020/4021/288; 692/420/2780/262; Analysis; Autoimmunity; Biomedicine; Cancer; Deoxyribonucleic acid; DNA; Gastroenterology; Gastrointestinal diseases; Gastrointestinal system; Health aspects; Hepatology; Histones; Leukocytes (neutrophilic); Liver; Medicine & Public Health; Metastases; Neutrophils; review-article; Thrombosis
• ISSN: 1759-5045; 1759-5053
• DOI: 10.1038/nrgastro.2017.183

Key Points Neutrophil extracellular traps (NETs) are extracellular structures composed of chromatin coated with histones, proteases and granular and cytosolic proteins that help catch and kill microorganisms Kupffer cells and neutrophils in the liver cooperate to eliminate pathogens in circulation NETs have a potential role in gastrointestinal infection and sepsis, whereas several pathogenic bacteria are capable of escaping or hijacking NET-mediated capturing and killing Excess NET formation is associated with the pathology of inflammatory liver and gastrointestinal diseases Exposure to components of NETs might generate autoantibodies in gastrointestinal autoimmune diseases and facilitate the inappropriate immune response Therapies that target key pathways in NET formation, with or without other treatments, might improve the treatment for gastrointestinal inflammatory diseases, cancer and thrombosis Neutrophil extracellular traps (NETs) have an important role during infection but they are also related to the exacerbation of inflammation and the development of autoimmunity, cancer metastasis and inappropriate thrombosis. Here, the authors focus on the role of NETs in the liver and gastrointestinal system, outlining their protective and pathological effects and their potential for therapeutic intervention. Neutrophil extracellular traps (NETs) have an important role during infection by helping neutrophils to capture and kill pathogens. However, evidence is accumulating that uncontrolled or excessive production of NETs is related to the exacerbation of inflammation and the development of autoimmunity, cancer metastasis and inappropriate thrombosis. In this Review, we focus on the role of NETs in the liver and gastrointestinal system, outlining their protective and pathological effects. The latest mechanistic insights in NET formation, interactions between microorganisms and NETs and the relationship between neutrophil subtypes and their functions are also discussed. Additionally, we describe the potential importance of NET-related molecules, including cell-free DNA and hypercitrullinated histones, as biomarkers and targets for therapeutic intervention in gastrointestinal diseases.