Fibrin is a key regulator of neutrophil effector function in the oral mucosal barrier

Plasmin is an abundant plasma protease that can cleave and inactivate the clot-associated protein fibrin

Humans lack plasmin and its inactive pro-enzyme form plasminogen (PLG), which can cause severe inflammation of mucosal tissues such as the mouth and eyes

However, the specific mechanism of mucosal barrier immunity remains to be elucidated

In the oral cavity, excessive extravascular fibrin is assumed to be associated with severe oral mucosal (gingival) inflammation, support bone (periodontal) destruction, and adolescent dentition loss and plasminogen deficiency

Consistent with the findings of plasminogen-deficient humans, plasminogen-deficient mice exhibited extravascular fibrin accumulation, gum inflammation, and periodontal bone loss

This indicates that the commensal microbial community is the triggering factor of oral mucosal fibrin deposition and related immunopathology

It is worth noting that the mutant fibrin expressed in plasminogen-deficient mice lacks a binding site for myeloid integrin alpha_riceβ₂Although the deposition of gingival fibrin and the accumulation of neutrophils remained unchanged, periodontal disease did not develop

These findings provide insights into the role of fibrin in neutrophil activation and oral mucosal immune function defects and normal fibrinolysis

Summarize

Tissue-specific cues are essential for the homeostasis of the mucosal barrier

Here, we report that the coagulation factor fibrin is a key regulator of neutrophil function in the oral mucosal barrier