Neutrophil extracellular traps and extracellular histones potentiate IL-17 inflammation in periodontitis

DOI PDF 被引用文献2件
  • Tae Sung Kim
    Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research 1 , , Bethesda, MD, USA
  • Lakmali M. Silva
    Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research 1 , , Bethesda, MD, USA
  • Vasileios Ionas Theofilou
    Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research 1 , , Bethesda, MD, USA
  • Teresa Greenwell-Wild
    Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research 1 , , Bethesda, MD, USA
  • Lu Li
    State University of New York at Buffalo, University at Buffalo 4 Department of Oral Biology, , Buffalo, NY, USA
  • Drake Winslow Williams
    Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research 1 , , Bethesda, MD, USA
  • Tomoko Ikeuchi
    Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research 1 , , Bethesda, MD, USA
  • Laurie Brenchley
    Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research 1 , , Bethesda, MD, USA
  • Thomas H. Bugge
    Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research 2 , , Bethesda, MD, USA
  • Patricia I. Diaz
    State University of New York at Buffalo, University at Buffalo 4 Department of Oral Biology, , Buffalo, NY, USA
  • Mariana J. Kaplan
    Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health 6 , Bethesda, MD, USA
  • Carmelo Carmona-Rivera
    Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health 6 , Bethesda, MD, USA
  • Niki M. Moutsopoulos
    Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research 1 , , Bethesda, MD, USA

抄録

<jats:p>Neutrophil infiltration is a hallmark of periodontitis, a prevalent oral inflammatory condition in which Th17-driven mucosal inflammation leads to destruction of tooth-supporting bone. Herein, we document that neutrophil extracellular traps (NETs) are early triggers of pathogenic inflammation in periodontitis. In an established animal model, we demonstrate that neutrophils infiltrate the gingival oral mucosa at early time points after disease induction and expel NETs to trigger mucosal inflammation and bone destruction in vivo. Investigating mechanisms by which NETs drive inflammatory bone loss, we find that extracellular histones, a major component of NETs, trigger upregulation of IL-17/Th17 responses, and bone destruction. Importantly, human findings corroborate our experimental work. We document significantly increased levels of NET complexes and extracellular histones bearing classic NET-associated posttranslational modifications, in blood and local lesions of severe periodontitis patients, in the absence of confounding disease. Our findings suggest a feed-forward loop in which NETs trigger IL-17 immunity to promote immunopathology in a prevalent human inflammatory disease.</jats:p>

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