{"doi":"10.1093/jimmun/vkaf283.233","title":"The critical role of fibrin-platelet aggregates in oral mucosal immunity: insights into neutrophil contributions 2298","abstract":"Abstract Description The mucosal immunity plays a vital role in defending against pathogens while maintaining tolerance to harmless antigens—an essential balance for homeostasis at barrier sites, where the hemostatic and inflammatory systems work together to modulate immunity. In periodontitis, an oral inflammatory disease causing gingiva and bone destruction, this balance is disrupted, leading to excessive inflammation. Plasminogen (Plg)-deficient patients manifest periodontitis, providing a great resource to study hemostatic factors in inflammation. Plg is the zymogen of plasmin, an active enzyme that removes extravascular fibrin deposits. Fibrin is proinflammatory unless removed in a timely manner. Using Plg-/- mice that phenocopy human disease, we have shown increased neutrophil accumulation near fibrin deposits, fibrin–αMβ2 engagement activates neutrophil effector functions, and drives immunopathology. However, mechanisms behind neutrophil recruitment remain poorly understood. Herein, we examine fibrin’s role in neutrophil recruitment using genetically engineered mouse models, histology, single-cell RNA sequencing, and flow cytometry. Initial findings in Plg-/- mice display differential gene expression in immune cells, with fibrin-platelet aggregates influencing immune cell recruitment. In conclusion, hemostatic factors mediate oral mucosal immunopathology by recruiting and activating immune cells and provide a basis for novel therapeutic strategies for treating mucosal diseases. Funding Sources This study was supported by an NIDCR grant R00DE030124 (PI: SILVA), Harvard School of Dental Medicine Fellowship in honor of Aina M. Auskaps, DMD award 2024 (Eleanor and Miles Shore Faculty Development Award), and HSDM start-up funds. Topic Categories Mucosal and Regional Immunology (MUC)","journal":"The Journal of Immunology","year":2025,"id":582617,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":624247,"name":"Lakmali M. Silva","orcid":"0000-0001-6282-2657","position":1,"is_corresponding":false},{"id":1495001,"name":"Lina Cathy Fellah","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:59.653747Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}