An emerging role for neutrophil extracellular traps in noninfectious disease

  title={An emerging role for neutrophil extracellular traps in noninfectious disease},
  author={Selina K Jorch and Paul Kubes},
  journal={Nature Medicine},
The production of neutrophil extracellular traps (NETs) is a process that enables neutrophils to help catch and kill bacteria. However, increasing evidence suggests that this process might also occur in noninfectious, sterile inflammation. In this Review, we describe the role of NETosis in autoimmunity, coagulation, acute injuries and cancer, and discuss NETs as potential therapeutic targets. Furthermore, we consider whether extracellular DNA is always detrimental in sterile inflammation and… 
Neutrophils and neutrophil extracellular traps in the liver and gastrointestinal system
  • M. Honda, P. Kubes
  • Biology, Medicine
    Nature Reviews Gastroenterology & Hepatology
  • 2018
The role of NETs in the liver and gastrointestinal system is focused on, outlining their protective and pathological effects and the potential importance of NET-related molecules, including cell-free DNA and hypercitrullinated histones, as biomarkers and targets for therapeutic intervention in gastrointestinal diseases is described.
Neutrophil Extracellular Traps in Autoimmune Diseases
Neutrophil extracellular traps deliver multiple autoantigens to host immune system that induce autoimmune responses and directly release damage‐associated molecular patterns to amplify inflammatory responses.
Neutrophil Extracellular Traps and Liver Disease.
There is much interest in the therapeutic potential of NET inhibition, but future clinical applications must be balanced against potential increased risk of infection.
Neutrophil Extracellular Traps: Formation and Involvement in Disease Progression.
The purpose of this review is to highlight the molecular mechanisms of NETosis and its antimicrobial effect and a current status ofNETosis in the pathogenesis of inflammatory and autoimmune disorders has been reviewed for better understanding.
Mechanisms and disease relevance of neutrophil extracellular trap formation
Current concepts of the mechanisms and disease relevance of NET formation are discussed and the disease relevance and clinical translatability of this unconventional cellular mechanism are discussed.
The immune regulatory role of neutrophils
New work suggests that it is time to give greater consideration to the anti‐inflammatory role of neutrophils, such as in the control of cytokine release during sepsis.
Neutrophil extracellular traps : function in infectious and non-Infectious conditions
Light is shed on the clearance and degradation of NETs by phagocytic cells and the involvement of several endonucleases in a cell type-specific manner, and the importance ofNETs in fungal killing is confirmed, with new evidence for a role of JAGN1 in this process.
The emerging role of neutrophilic extracellular traps in intestinal disease
The latest knowledge on the formation mechanisms of NETs and their pathophysiological roles in a variety of intestinal diseases are summarized with the aim of providing an essential directional guidance and theoretical basis for clinical interventions in the exploration of mechanisms underlyingNETs and targeted therapies.
On the Origin of Neutrophil Extracellular Traps in COVID-19
The aim of this review is to summarize potential inducers of NETs formation in severe COVID-19 and to discuss potential treatment options targetingNETs formation of removal.
Neutrophil Extracellular Traps Tied to Rheumatoid Arthritis: Points to Ponder
The potential of neutrophil extracellular traps to drive the pathogenesis of rheumatoid arthritis and experimental animal models is summarized.


NETosis: how vital is it?
The evidence that neutrophil extracellular traps (NETs) play a critical role in innate immunity is examined and how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release is examined.
Gastrointestinal cancer: Neutrophils and cancer: guilt by association
  • C. Jenne, P. Kubes
  • Medicine, Biology
    Nature Reviews Gastroenterology &Hepatology
  • 2016
Findings provide novel insights into the role of neutrophils in cancer and suggest enticing directions for future research.
Neutrophil Extracellular Traps Kill Bacteria
It is described that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria, which degrade virulence factors and kill bacteria.
Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis
This study provides a mechanistic explanation for the tumour-promoting effects of hypercoagulation, which could be used as a new biomarker or as a therapeutic target.
NETosis: a new factor in tumor progression and cancer-associated thrombosis.
It is proposed that the rapid developments in the field of NETosis may provide new targets to combat the thrombotic consequences of cancer and perhaps even help to contain the disease itself.
Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines
It is reported that neutrophils recruited to sites of inflammation undergo oxidative burst and form neutrophil extracellular traps (NETs), and aggregated NETs promote the resolution of neutrophilic inflammation by degrading cytokines and chemokines and disrupting neutrophIL recruitment and activation.
Neutrophil elastase‐deficient mice form neutrophil extracellular traps in an experimental model of deep vein thrombosis
Neutrophil elastase deficiency had no significant effect on thrombosis in the inferior vena cava stenosis model and is not required for mouse neutrophil NET production in vitro with non‐infectious stimuli.
Signal Inhibitory Receptor on Leukocytes-1 Limits the Formation of Neutrophil Extracellular Traps, but Preserves Intracellular Bacterial Killing
Signal inhibitory receptor on leukocytes-1 (SIRL-1) attenuates NET release by human neutrophils in response to distinct triggers, including opsonized Staphylococcus aureus and inflammatory danger signals, and is defined as an intervention point of benefit to suppress NET formation in disease while preserving intracellular antimicrobial defense.
Extracellular histones in tissue injury and inflammation
Extracellular histones contribute to the microvascular complications of sepsis, major trauma, small vessel vasculitis as well as acute liver, kidney, brain, and lung injury and prevent the degradation of extracellular DNA, which promotesautoimmunization, anti-nuclear antibody formation, and autoimmunity in susceptible individuals.
Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease
Findings highlight a role for mitochondria in the generation not only of NETs but also of pro-inflammatory oxidized mitochondrial DNA in autoimmune diseases.