Niki Moutsopoulos

Primary immunodeficiencies reveal the essential role of tissue neutrophils in periodontitis

Publisher: Wiley

Date: 18-12-2019

DOI: 10.1111/IMR.12724

Neutrophils are gatekeepers of mucosal immunity

Publisher: Wiley

Date: 20-11-2022

DOI: 10.1111/IMR.13171

Abstract: Mucosal tissues are constantly exposed to the outside environment. They receive signals from the commensal microbiome and tissue‐specific triggers including alimentary and airborne elements and are tasked to maintain balance in the absence of inflammation and infection. Here, we present neutrophils as sentinel cells in mucosal immunity. We discuss the roles of neutrophils in mucosal homeostasis and overview clinical susceptibilities in patients with neutrophil defects. Finally, we present concepts related to specification of neutrophil responses within specific mucosal tissue microenvironments.

Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier.

Publisher: American Association for the Advancement of Science (AAAS)

Date: 24-12-2021

DOI: 10.1126/SCIENCE.ABL5450

Abstract: Plasmin is an abundant plasma protease that cleaves and deactivates the clot-associated protein fibrin. Human deficiencies in plasmin and its inactive proenzyme form, plasminogen (PLG), cause severe inflammation in mucosal tissues such as the mouth and eyes. Silva et al . report that, like humans, mice lacking plasminogen accumulate extravascular fibrin and develop an oral pathology that phenocopies human ligneous periodontitis (see the Perspective by Vicanolo and Hidalgo). The excess fibrin activates neutrophils through the αMβ2 (Mac-1) integrin receptor, which triggers the production of reactive oxygen species and neutrophil extracellular traps. Additionally, certain human polymorphisms in the PLG gene were found to be associated with increased likelihood of developing periodontitis, suggesting that fibrin–neutrophil interactions may be an attractive target for future treatments of this prevalent disease. —STS

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

Publisher: Rockefeller University Press

Date: 06-2023

DOI: 10.1084/JEM.20221751

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.

Aristotle University Of Thessaloniki

Location: Greece

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University Of Maryland, Baltimore

Location: United States of America

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National Institutes Of Health

Location: United States of America

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Universtiy Of Maryland

Location: United States of America

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