Fibrin is a critical regulator of neutrophil effector function at mucosal barrier sites
Silva, L. M.; Doyle, A. D.; Tran, C. L.; Greenwell-Wild, T.; Dutzan, N.; Lum, A. G.; Agler, C. S.; Sibree, M.; Jani, P.; Martin, D.; Kram, V.; Castellino, F. J.; Flick, M. J.; Divaris, K.; Bugge, T. H.; Moutsopoulos, N. M.
Show abstract
Tissue-specific cues are critical for homeostasis at mucosal barriers. Here, we document that the clotting factor fibrin is a critical regulator of neutrophil function at mucosal barriers. We demonstrate that fibrin engages neutrophils through the M{beta}2 integrin receptor and activates effector functions, including the production of reactive oxygen species and NET formation. These immune-protective neutrophil functions become tissue damaging in the context of impaired plasmin-mediated fibrinolysis. Indeed, the accumulation of fibrin due to Mendelian genetic defects in plasmin leads to severe oral mucosal immunopathology in mice and humans. Concordantly, genetic polymorphisms in the human PLG gene, encoding plasminogen, are associated with common forms of the oral mucosal disease periodontitis. Our work uncovers fibrin as a critical regulator of neutrophil effector function within the mucosal tissue microenvironment and suggests fibrin-neutrophil engagement as a pathogenic instigator and therapeutic target in common mucosal disease.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Treponema denticola dentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells 93%
- Mitochondrial ROS production by neutrophils is required for host antimicrobial function against Streptococcus pneumoniae and is controlled by A2B adenosine receptor signaling 91%
- Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils 91%
Similar papers in this journal
- The Implant-Induced Foreign Body Response is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins 94%
- Osteopontin and iCD8α cells promote intestinal intraepithelial lymphocytes homeostasis 91%
- The IRE1α stress signaling axis is a key regulator of neutrophil antimicrobial effector function 91%
Similar papers in this journal
- Panton-Valentine leukocidin-induced neutrophil extracellular traps lack antimicrobial activity and are readily induced in patients with recurrent PVL+-Staphylococcus aureus infections 92%
- Streptococcus anginosus Activates the NLRP3 Inflammasome to Promote Inflammatory Responses from Macrophages 92%
- Macrophage Inflammatory State Influences Susceptibility to Lysosomal Damage 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.