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The role of neutrophil extracellular traps in rheumatic diseases

Abstract

Rheumatic diseases are a collection of disorders defined by the presence of inflammation and destruction of joints and internal organs. A common feature of these diseases is the presence of autoantibodies targeting molecules commonly expressed in neutrophils. These preformed mediators are released by neutrophils but not by other immune cells such as macrophages. Neutrophils, major players in the host innate immune response, initiate a cell death mechanism termed neutrophil extracellular trap (NET) formation as a way to ensnare pathogens. NETs are also a source of released self-molecules found in rheumatic diseases. Subsequently, research on the role of NETs in the onset, progression and resolution of inflammation in rheumatic diseases has intensified. This Review has two aims. First, it aims to highlight the mechanisms required for the generation of NETs, the research landscape of which is rapidly changing. Second, it aims to discuss the role of neutrophils and NETs in systemic lupus erythematosus, vasculitis (specifically anti-neutrophil cytoplasmic autoantibody-associated vasculitis), rheumatoid arthritis and gout. Our goal is to clarify the field of NET research in rheumatic diseases in the hope of improving the therapeutic approaches utilized for these diseases.

Key points

  • Molecules released during neutrophil extracellular trap (NET) formation can often become autoantigens in systemic lupus erythematosus, small vessel vasculitis, rheumatoid arthritis and gout.

  • Damaged tissues and organs in these rheumatic diseases are prone to containing NET-derived material.

  • Neutrophils from patients with some rheumatic diseases spontaneously undergo NETosis in vitro, reflecting the pre-activation of neutrophils during chronic inflammation.

  • To date, whether NET formation is deleterious to progression of all rheumatic diseases is unclear.

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Fig. 1: Neutrophil extracellular trap induction in human neutrophils.
Fig. 2: The role of neutrophil extracellular traps in rheumatic diseases.

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Nature Reviews Rheumatology thanks M. Herrmann, M. Radic and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Apel, F., Zychlinsky, A. & Kenny, E.F. The role of neutrophil extracellular traps in rheumatic diseases. Nat Rev Rheumatol 14, 467–475 (2018). https://doi.org/10.1038/s41584-018-0039-z

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