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Extracellular DNA traps in inflammation, injury and healing

Abstract

Following strong activation signals, several types of immune cells reportedly release chromatin and granular proteins into the extracellular space, forming DNA traps. This process is especially prominent in neutrophils but also occurs in other innate immune cells such as macrophages, eosinophils, basophils and mast cells. Initial reports demonstrated that extracellular traps belong to the bactericidal and anti-fungal armamentarium of leukocytes, but subsequent studies also linked trap formation to a variety of human diseases. These pathological roles of extracellular DNA traps are now the focus of intensive biomedical research. The type of pathology associated with the release of extracellular DNA traps is mainly determined by the site of trap formation and the way in which these traps are further processed. Targeting the formation of aberrant extracellular DNA traps or promoting their efficient clearance are attractive goals for future therapeutic interventions, but the manifold actions of extracellular DNA traps complicate these approaches.

Key points

  • Extracellular traps survey ducts and vessels under normal physiological conditions, immobilize and sequester pathogens during host defence and shield viable tissue from necrotic areas in the context of massive tissue injury.

  • Extracellular traps tend to aggregate and form larger functional units endowed with a plethora of enzymatic activities that can modify biomolecules at the site of inflammation.

  • Extracellular traps participate in both the initiation and in the resolution of inflammation.

  • Extracellular traps that escape clearance in the body might challenge immune tolerance and serve as autoantigen repositories that trigger the onset and promote the chronicity of autoimmune diseases.

  • Interfering with the formation or clearance of extracellular traps might create novel therapeutic interventions for inflammation and tissue injury.

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Fig. 1: Types of NETs and aggregate NETs.
Fig. 2: Microscopic visualization of NETs.
Fig. 3: Cell composition over time during an inflammatory response.
Fig. 4: NETs in renal disease.

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Acknowledgements

The authors’ work was partially supported by the German Research Foundation (DFG) (CRC1181 projects C03, A01 and Z02 and TRR241-B04), by the Innovative Medicines Initiative (IMI)-funded RTCure and by Ardea Biosciences, Inc.

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Nature Reviews Nephrology thanks P. Migliorini, and the other anonymous reviewer(s), for their contribution to the peer review of this work.

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All authors contributed equally to this review. M.H. researched data for the article.

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Correspondence to Martin Herrmann.

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Daniel, C., Leppkes, M., Muñoz, L.E. et al. Extracellular DNA traps in inflammation, injury and healing. Nat Rev Nephrol 15, 559–575 (2019). https://doi.org/10.1038/s41581-019-0163-2

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