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  • Review Article
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The role of neutrophils and NETosis in autoimmune and renal diseases

Nature Reviews Nephrology volume 12, pages 402–413 (2016)Cite this article

Subjects

Key Points

  • Neutrophils may have critical roles in the pathogenesis of autoimmune diseases by forming neutrophil extracellular traps (NETs), secreting proinflammatory cytokines and by directly causing tissue damage

  • NET formation externalizes autoantigens that might contribute to the pathophysiology and clinical manifestations of autoimmune diseases, either directly or by modulating other components of the immune system

  • An imbalance in NET formation and degradation might increase the half-life of NET products and augment the immune response

  • Novel therapies that target key pathways in neutrophil function and NET formation might improve the treatment of autoimmune diseases.

Abstract

Systemic autoimmune diseases are a group of disorders characterized by a failure in self-tolerance to a wide variety of autoantigens. In genetically predisposed individuals, these diseases occur as a multistep process in which environmental factors have key roles in the development of abnormal innate and adaptive immune responses. Experimental evidence collected in the past decade suggests that neutrophils — the most abundant type of white blood cell — might have an important role in the pathogenesis of these diseases by contributing to the initiation and perpetuation of immune dysregulation through the formation of neutrophil extracellular traps (NETs), synthesis of proinflammatory cytokines and direct tissue damage. Many of the molecules externalized through NET formation are considered to be key autoantigens and might be involved in the generation of autoimmune responses in predisposed individuals. In several systemic autoimmune diseases, the imbalance between NET formation and degradation might increase the half-life of these lattices, which could enhance the exposure of the immune system to modified autoantigens and increase the capacity for NET-induced organ damage. This Review details the role of neutrophils and NETs in the pathophysiology of systemic autoimmune diseases, including their effect on renal damage, and discusses neutrophil targets as potential novel therapies for these diseases.

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Figure 1: NETosis pathways and potential therapeutic targets.
Figure 2: NETs in low-density granulocytes.
Figure 3: Neutrophils and NETosis in the pathogenesis of autoimmune and renal diseases.

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  1. National Institute of Arthritis and Musculoskeletal and Skin Diseases, Systemic Autoimmunity Branch, Intramural Research Program, National Institutes of Health, Room 6D 47C, 10 Center Drive, Bethesda, 20892–1930, MD, USA

    Sarthak Gupta & Mariana J. Kaplan

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M.J.K. and S.G. researched the data for the article, discussed its content and wrote the Review. M.J.K. reviewed and edited the manuscript before submission.

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Gupta, S., Kaplan, M. The role of neutrophils and NETosis in autoimmune and renal diseases. Nat Rev Nephrol 12, 402–413 (2016). https://doi.org/10.1038/nrneph.2016.71

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