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IMMUNOLOGY IN 2019

NETs spread ever wider in rheumatic diseases

Dysregulation in the formation and/or clearance of neutrophil extracellular traps (NETs) is important in immune dysregulation and organ damage in chronic inflammatory conditions. Studies in 2019 have shown how certain genetic susceptibilities to autoimmunity can promote NET-mediated inflammation, and expanded the role for NETs in vascular damage and premature atherosclerosis.

Key advances

  • Genetic risk alleles for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are functionally linked to increased peptidylarginine deiminase 4 expression and enhanced neutrophil extracellular trap (NET) formation2.

  • Insights into the monogenic autoinflammatory disease deficiency of adenosine deiminase 2 (DADA2) link adenosine metabolism with neutrophil activation, NET formation and pathogenic inflammatory cascades3.

  • Histone H4, which is present in NETs, is involved in plaque destabilization in atherosclerosis, an important co-morbidity of RA and SLE4.

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Fig. 1: New insights into NET formation and the role of NETs in disease states.

References

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Acknowledgements

The work of the authors is supported financially by the Intramural Research Program at the US National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (to M.J.K.) and by the Swedish Research Council (to G.W.).

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Correspondence to Mariana J. Kaplan.

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The authors declare no competing interests.

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Wigerblad, G., Kaplan, M.J. NETs spread ever wider in rheumatic diseases. Nat Rev Rheumatol 16, 73–74 (2020). https://doi.org/10.1038/s41584-019-0352-1

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