Fibrin is a critical regulator of neutrophil effector function at mucosal barrier sites

Plasminogen (Plg), the zymogen precursor of the serine protease plasmin, is synthesized by the liver and is present in high concentration in the circulation and in interstitial fluids to provide focal proteolysis, after being converted to plasmin by urokinase or tissue plasminogen activator. Homozygous or compound heterozygous mutations in the human Plg gene (PLG) typically lead to severe mucosal disease involvement suggesting, a critical role for this gene/pathway in mucosal immunity. Indeed, such patients present with deposition of fibrin at various mucosal sites leading to ocular disease (conjunctivitis), oral mucosal disease (ligneous periodontitis), lung, vaginal and gastrointestinal tract involvement. In the oral mucosa, local deposition of fibrin is hypothesized to lead to severe soft tissue and bone destruction around teeth and often loss of the entire dentition in adolescence. Mucosal inflammation in areas surrounding the dentition and destruction of underlying bone are also the hallmarks of the common human oral mucosal disease, periodontitis. Plg-deficient mice phenocopy the human disease and we aim to use this animal model to understand the mechanism underlying fibrin-mediated periodontal immunopathology in vivo. Herein, we analyse the transcriptome of gingival tissues extracted from Plg-deficient mice in comparison to their wild-type littermates at 12 weeks of age. Examine the changes in the transcriptome in oral mucosal tissues of Plg-deficient mice compared with wild-type littermates.