Neutrophil extracellular traps (NETs) are a well described form of neutrophil cell death which releases extracellular DNA decorated with enzymes, proteases, histones and reactive oxygen species. There is now accumulating evidence that this form of cell death is not unique to neutrophils. It has been discovered that macrophages, monocytes, mast cells, eosinophils, basophils, and lymphocytes (both B and T cells), have all been found to release extracellular DNA inducing inflammatory responses.
We now know in the context of autoimmunity, COVID-19, cancer, thrombosis and generalized inflammation that unregulated NETs are pathogenic. This can lead to an injurious release of enzymes and proteases, damaging surrounding epithelial and endothelial cells. It also causes the release of over 70 known autoantigens. The release of this DNA, normally protected within the nucleus, activates intracellular DNA sensors, such as signaling effector stimulator of interferon genes (STING), DNA sensing receptor cyclic GMP-AMP synthase (cGAS) and endosomal Toll-like receptor 9 (TLR9), leading to activation of Nuclear factor kappa-light chain enhancer of activated B cells (NFkB) and the release of pro inflammatory cytokines.
In this Research Topic it is our goal to highlight the different pathogenic mechanisms of extracellular trap release from leukocytes in both animal models of diseases and patient cohorts from diseases where leukocytic extracellular traps (organ specific or systemically) are shown to be associated with worse disease outcomes. Recently extracellular trap like release from B cells and T cells has been described to induce inflammatory responses. The mechanism behind this type of cell death in non-innate cells is yet to be fully investigated. The overall aim is to collate data which will provide a better understanding of the different stimuli that induce extracellular trap release from leukocytes. We also hope to elucidate it’s inflammatory mechanisms, identify new methods of detection, provide novel analysis of leucocyte extracellular traps, and identify potential therapeutic agents which inhibit critical components or pathways, limiting DNA release from leukocytes.
We welcome research in the fields of autoimmunity, inflammation, cancer and thrombosis to describe the role of different leukocyte extracellular traps. We welcome the submission of Original Research, Case Report, Review, Mini-review and Perspective articles related to but not limited to, the following subtopics:
1. The analysis of different patient populations of either peripheral blood mononuclear and multinuclear cells to various extracellular trap inducing stimuli, in a disease context
2. In vitro inhibition studies targeting pivotal mechanisms to prevent the release of extracellular traps
3. In vivo animal models of disease where extracellular traps are implicated in the progression of pathogenesis
4. In vitro studies of inflammatory mechanisms exerted by extracellular traps
5. Novel analysis or detection of extracellular traps
6. Role and mechanisms of extracellular trap release from neutrophils as well as other leukocyte subsets, including T cells, B cells, monocytes and macrophages
Neutrophil extracellular traps (NETs) are a well described form of neutrophil cell death which releases extracellular DNA decorated with enzymes, proteases, histones and reactive oxygen species. There is now accumulating evidence that this form of cell death is not unique to neutrophils. It has been discovered that macrophages, monocytes, mast cells, eosinophils, basophils, and lymphocytes (both B and T cells), have all been found to release extracellular DNA inducing inflammatory responses.
We now know in the context of autoimmunity, COVID-19, cancer, thrombosis and generalized inflammation that unregulated NETs are pathogenic. This can lead to an injurious release of enzymes and proteases, damaging surrounding epithelial and endothelial cells. It also causes the release of over 70 known autoantigens. The release of this DNA, normally protected within the nucleus, activates intracellular DNA sensors, such as signaling effector stimulator of interferon genes (STING), DNA sensing receptor cyclic GMP-AMP synthase (cGAS) and endosomal Toll-like receptor 9 (TLR9), leading to activation of Nuclear factor kappa-light chain enhancer of activated B cells (NFkB) and the release of pro inflammatory cytokines.
In this Research Topic it is our goal to highlight the different pathogenic mechanisms of extracellular trap release from leukocytes in both animal models of diseases and patient cohorts from diseases where leukocytic extracellular traps (organ specific or systemically) are shown to be associated with worse disease outcomes. Recently extracellular trap like release from B cells and T cells has been described to induce inflammatory responses. The mechanism behind this type of cell death in non-innate cells is yet to be fully investigated. The overall aim is to collate data which will provide a better understanding of the different stimuli that induce extracellular trap release from leukocytes. We also hope to elucidate it’s inflammatory mechanisms, identify new methods of detection, provide novel analysis of leucocyte extracellular traps, and identify potential therapeutic agents which inhibit critical components or pathways, limiting DNA release from leukocytes.
We welcome research in the fields of autoimmunity, inflammation, cancer and thrombosis to describe the role of different leukocyte extracellular traps. We welcome the submission of Original Research, Case Report, Review, Mini-review and Perspective articles related to but not limited to, the following subtopics:
1. The analysis of different patient populations of either peripheral blood mononuclear and multinuclear cells to various extracellular trap inducing stimuli, in a disease context
2. In vitro inhibition studies targeting pivotal mechanisms to prevent the release of extracellular traps
3. In vivo animal models of disease where extracellular traps are implicated in the progression of pathogenesis
4. In vitro studies of inflammatory mechanisms exerted by extracellular traps
5. Novel analysis or detection of extracellular traps
6. Role and mechanisms of extracellular trap release from neutrophils as well as other leukocyte subsets, including T cells, B cells, monocytes and macrophages