期刊
AUTOIMMUNITY REVIEWS
卷 18, 期 8, 页码 751-760出版社
ELSEVIER
DOI: 10.1016/j.autrev.2019.06.011
关键词
Trained immunity; Neutrophil extracellular traps; NET formation; Systemic lupus Erythematosus; ANCA-associated vasculitides; Thromboinflammation; Fibrosis
类别
资金
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [742390]
- European Union's Horizon 2020 research and innovation programme [733100]
- FOREUM Foundation for Research in Rheumatology
- Hellenic Society of Rheumatology
- H2020 Societal Challenges Programme [733100] Funding Source: H2020 Societal Challenges Programme
Neutrophils derive from hematopoietic stem cells (HSCs) with systemic inflammation driving their activation and differentiation to myeloid progenitors to ensure enhanced myelopoiesis. Epigenetic reprograming and reeducation of these HSCs produces neutrophils primed towards elimination of pathogens and increased inflammatory response. Neutrophils-an important component of acute inflammation- are not present in chronic inflammatory tissues leading to the false assumption that they may not be as important for the latter. Activated neutrophils may release Neutrophil Extracellular Traps (NETs) during a distinct form of cell death, named NETosis; NETs are rich in bioactive molecules that promote thrombosis (including atherothrombosis), inflammation and fibrosis. Thus, although neutrophils may not be present in chronic inflammatory lesions, their remnants may amplify the inflammatory response beyond their short life-span in the tissues. Herein, we review current evidence supporting a role of neutrophils and NETosis in tissue injury and dysfunction in systemic autoimmunity using as disease paradigms Systemic Lupus Erythematosus (SLE) and the ANCA-associated vasculitides (AAV). We also discuss the mechanisms involved and their potential as targets for novel therapy and drug repositioning.
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