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What good can neutrophils do in UC?
  1. Azucena Salas
  1. IDIBAPS, CIBERehd, Hospital Clinic de Barcelona, Barcelona, Spain
  1. Correspondence to Dr Azucena Salas, IDIBAPS, CIBERehd, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain; ASALAS1{at}

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Neutrophils are essential for limiting the translocation of bacteria when mucosal surfaces are breached. Among other antimicrobial mechanisms, neutrophils can release neutrophil extracellular traps (NETs), which are web-like extracellular structures containing cytosolic and granule proteins assembled on a network of decondensed chromatin. Formation of NETs is dependent on the activity of peptidyl-arginine deiminases (PAD), in particular, PAD4, an enzyme that catalyses the citrullination of histones and promotes chromatin decondensation.1 While limiting bacterial and fungal dissemination, NETs—like other neutrophil effector mechanisms—can contribute to the pathogenesis of immune-mediated diseases, including UC. The ability of NETs to damage tissues is well documented in infection and sterile disease. Indeed, previous evidence has shown the beneficial effects of PAD4 inhibitors, or of treatment with DNAse, in models of colitis, making these molecules attractive new targets with anti-inflammatory potential.2

In Gut, Leppkes and collaborators contradict this dogma and describe the unexpected protective role of those NETs that participate in homeostasis and reduce the bleeding of intestinal ulcers.3 This effect is dependent on the activity of PAD4, as shown by PAD4-deficient mice, which suffer from increased mucosal damage and disease severity in experimental models of wound healing and colitis. These results, which challenge the previous hypothesis that …

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  • Contributors AS researched and wrote the commentary,

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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