Year: 2024
Type: article
Abstract: Tissue-specific cues are critical for homeostasis at mucosal barriers. Here, we report that the clotting factor fibrin is a critical regulator of neutrophil function at the oral mucosal barrier. We demonstrate that commensal microbiota trigger extravascular fibrin deposition in the oral mucosa. Fibrin engages neutrophils through the aMb2 integrin receptor and activates effector functions, including the production of reactive oxygen species and neutrophil extracellular trap formation. These immune-protective neutrophil functions become tissue damaging in the context of impaired plasmin-mediated fibrinolysis in mice and humans. Concordantly, genetic polymorphisms in PLG, encoding plasminogen, are associated with common forms of periodontal disease. Thus, fibrin is a critical regulator of neutrophil effector function, and fibrin-neutrophil engagement may be a pathogenic instigator for a prevalent mucosal disease.
DOI: 10.17615/mw75-hr03
Authors: Dutzan N., Abusleme L., Flick M.J., Kastrup C.J., Moss K., Lionakis M.S., Juang L.J., Chun E.M., Leung J., Bugge T.H., Moutsopoulos N.M., Kram V., Sibree M., Castellino F.J., Agler C.S., Lum A.G., Silva L.M., Jani P., Zuazo C.E., Divaris K., Greenwell-Wild T., Doyle A.D., Martin D., Tran C.L.
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1308944910, Thrombin-dependent mechanisms of pancreatic ductal adenocarcinoma disease, G2631077758, G4477607614, G4673630154, Fibrin(ogen) control of metabolic inflammation and obesity, Genome-Wide Association Study of Early Childhood Caries, G9000105713, NIDCR Annual Reports - Veterinary Resources Core, Genomic and Computational Biology Support for NIDCD Intramural Research, NIDCR DIR Scientific Cores (Combined Technical Research Core)
OpenAlex ID: W4400023325