De novo DUOX2 expression in neutrophil subsets shapes the pathogenesis of intestinal disease

• 成果类型: Article
• 署名作者: Singh, Ashish K.; Ainciburu, Marina; Wynne, Kieran; Bhat, Sajad A.; Blanco, Alfonso; Tzani, Ioanna; Akiba, Yasutada; Lalor, Stephen J.; Kaunitz, Jonathan; Bourke, Billy; Kelly, Vincent P.; Doherty, Glen A.; Zerbe, Christa S.; Clarke, Colin; Hussey, Seamus; Knaus, Ulla G.
• 署名单位: University College Dublin; University College Dublin; University College Dublin; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Greater Los Angeles Healthcare System; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; National Children's Research Centre (NCRC); Trinity College Dublin; University College Dublin; Saint Vincent's University Hospital; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University College Dublin; Royal College of Surgeons - Ireland
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8483
• DOI: 10.1073/pnas.2421747122
• 发表日期: 2025-05-13
• 关键词: nadph oxidase; extracellular-matrix; cross-linking; h2o2

摘要

Infiltrating neutrophils are key effector cells in inflammatory bowel disease (IBD) while providing antimicrobial defense and tissue restitution in the intestine. The complexity of neutrophil functions in local environments underscores our limited understanding of how their adaptation in tissues influences disease progression. Here, we demonstrate that neutrophils recruited in murine colitis and infection models, idiopathic IBD, and gramming, resulting in the emergence of neutrophil populations that feature unique NADPH oxidase in both colitis and intestinal infection. Niche- directed reprogramming promoted a DUOX2- dependent chemokine and cytokine- rich intestinal environment that amplified and prolonged inflammatory responses, suggesting that selectively supAltering spatiotemporal redox signaling by de novo expression of a ROS- generating enzyme represents an important feature for functional neutrophil diversification in disease, with implications for other neutrophil- driven diseases in specialized niches.