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

Autor:	Kim TS; Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA., Silva LM; Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA.; Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA., Theofilou VI; Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA.; Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD, USA., Greenwell-Wild T; Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA., Li L; Department of Oral Biology, State University of New York at Buffalo, University at Buffalo, Buffalo, NY, USA., Williams DW; Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA., Ikeuchi T; Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA., Brenchley L; Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA., Bugge TH; Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA., Diaz PI; Department of Oral Biology, State University of New York at Buffalo, University at Buffalo, Buffalo, NY, USA., Kaplan MJ; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD, USA., Carmona-Rivera C; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD, USA., Moutsopoulos NM; Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research , National Institutes of Health, Bethesda, MD, USA.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2023 Sep 04; Vol. 220 (9). Date of Electronic Publication: 2023 Jun 01.
DOI:	10.1084/jem.20221751
Abstrakt:	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. (© 2023 Moutsopoulos et al.)
Databáze:	MEDLINE
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