Neutrophils in the Pathogenesis of Rheumatic Diseases: Fueling the Fire
- 31 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Clinical Reviews in Allergy & Immunology
- Vol. 60 (1), 1-16
- https://doi.org/10.1007/s12016-020-08816-3
Abstract
Systemic rheumatic diseases are a heterogeneous group of disorders characterized by profound immune dysregulation. Recent discoveries have led to a significant resurgence of interest in neutrophils as shapers of immune dysregulation and as triggers of organ damage in rheumatic diseases. Neutrophils contribute to the initiation, promotion, and perpetuation of immune dysregulation through a variety of mechanisms including synthesis of proinflammatory cytokines, direct tissue damage through degranulation and synthesis of reactive oxygen species, and the formation of neutrophil extracellular traps (NETs). The identification of a subset of proinflammatory neutrophils, the low-density granulocytes (LDGs), which promote Th1 responses and cause endothelial dysfunction, has further strengthened the pathogenic role of neutrophils in various rheumatic diseases. The presence of autoantibodies targeting molecules commonly expressed in neutrophils suggests that neutrophils, particularly NETs, may be a source of autoantigens. An imbalance between NET formation and degradation, which leads to increased NET levels in the circulation and tissues, could enhance the exposure of the immune system to modified autoantigens, promote vascular disease, and increase tissue damage. This review will present an overview of recent advances in our understanding of how neutrophil dysregulation modulates the innate and adaptive immune responses in systemic rheumatic diseases and their putative contributions to pathogenicity. Understanding the potential pathogenic role of neutrophil dysregulation may provide better molecular candidates for therapeutic targeting, and ultimately promote improvements in the clinical outcomes in rheumatic diseases.Keywords
Funding Information
- National Natural Science Foundation of China (81971521)
- Research and Development Institute, Silpakorn University (RDY2019-14)
- National Institute of Health (ZIAAR041199)
This publication has 163 references indexed in Scilit:
- B cell–helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleenNature Immunology, 2011
- Netting Neutrophils Are Major Inducers of Type I IFN Production in Pediatric Systemic Lupus ErythematosusScience Translational Medicine, 2011
- Neutrophils Activate Plasmacytoid Dendritic Cells by Releasing Self-DNA–Peptide Complexes in Systemic Lupus ErythematosusScience Translational Medicine, 2011
- PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular trapsThe Journal of Experimental Medicine, 2010
- Impairment of neutrophil extracellular trap degradation is associated with lupus nephritisProceedings of the National Academy of Sciences of the United States of America, 2010
- Transcription of proteinase 3 and related myelopoiesis genes in peripheral blood mononuclear cells of patients with active Wegener's granulomatosisArthritis & Rheumatism, 2010
- Novel expression signatures identified by transcriptional analysis of separated leucocyte subsets in systemic lupus erythematosus and vasculitisAnnals Of The Rheumatic Diseases, 2009
- Netting neutrophils in autoimmune small-vessel vasculitisNature Medicine, 2009
- Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory DiseaseAnnual Review of Immunology, 2009
- Neutrophil Extracellular Traps Kill BacteriaScience, 2004