한빛사논문
- 조회664
Tae Sung Kim 1, Lakmali M Silva 1,2, Vasileios Ionas Theofilou 1,3, Teresa Greenwell-Wild 1, Lu Li 4, Drake Winslow Williams 1, Tomoko Ikeuchi 1, Laurie Brenchley 1; NIDCD/NIDCR Genomics and Computational Biology Core; Thomas H Bugge 2, Patricia I Diaz 4, Mariana J Kaplan 5, Carmelo Carmona-Rivera 5, Niki M Moutsopoulos 1
1Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA.
2Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA.
3Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD, USA.
4Department of Oral Biology, State University of New York at Buffalo, University at Buffalo, Buffalo, NY, USA.
5Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD, USA.
Correspondence to Niki M. Moutsopoulos
Abstract
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.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-06-19)
- 국외 연구진
- 생명과학 > 면역학
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