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Review
. 2020 Jan;32(1):64-70.
doi: 10.1097/BOR.0000000000000667.

Deadliest catch: neutrophil extracellular traps in autoimmunity

Rishi R Goel  1 , Mariana J Kaplan
Affiliations
Review

Deadliest catch: neutrophil extracellular traps in autoimmunity

Rishi R Goel et al. Curr Opin Rheumatol. 2020 Jan.

Abstract

Purpose of review: To summarize recent evidence on the pathogenic effects of neutrophils and neutrophil extracellular traps (NETs) in autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis.

Recent findings: NETs can orchestrate innate and adaptive immune dysregulation through diverse mechanisms. NETs induce potent inflammatory responses and represent sources of many autoantigens, creating a feed-forward loop that may perpetuate disease and lead to organ damage. NETs are also increasingly relevant in atherosclerosis and could contribute to the increased risk of premature cardiovascular disease in patients with autoimmunity.

Summary: NET formation is increased in a variety of autoimmune and autoinflammatory diseases and can have remarkable effects on cell and tissue-specific damage. Novel therapeutics that target NET formation or clearance is a promising strategy for clinical management of autoimmune diseases and may prevent chronic complications associated with these conditions.

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Conflict of interest statement

Conflicts of interest:

There are no conflicts of interest.

Figures

Figure 1.
Figure 1.. NETs orchestrate innate and adaptive autoimmune responses in SLE.
NETs can induce type I interferon production by pDCs and other cell types and pro-inflammatory cytokine production by macrophages. NETs can also activate memory B cells, leading to autoantibody production that activates pDCs and further induces NET formation. NETs may be important in T cell priming; however, the interaction between NETs and antigen presenting cells (APCs) in SLE requires further investigation.
Figure 2.
Figure 2.. NET promote pathogenic immunity and amplify inflammation in rheumatoid arthritis.
NETs can induce pro-inflammatory cytokines in FLS. Citrullinated NET proteins can also be internalized by FLS and presented to Ag-specific CD4+ T cells, promoting ACPA production by autoreactive B cells. ACPAs can form immune complexes that stimulate synovial macrophages to produce pro-inflammatory cytokines. These cytokines and immune complexes further induce NET formation, creating a feed-forward loop that promotes autoimmunity.
See this image and copyright information in PMC

References

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