{"doi":"10.4049/jimmunol.2100903","title":"CD47 Promotes Autoimmune Valvular Carditis by Impairing Macrophage Efferocytosis and Enhancing Cytokine Production","abstract":"Abstract Systemic autoantibody-mediated diseases accelerate chronic cardiovascular disease in humans. In the K/B.g7 mouse model of spontaneous autoantibody-mediated inflammatory arthritis, valvular carditis arises in part because of Fc receptor–mediated activation of macrophages, leading to production of pathogenic TNF and IL-6. In this study, we explored whether impaired efferocytosis mediated by the interaction of CD47-expressing apoptotic cells with signal regulatory protein α (SIRPα) on macrophages contributes to disease progression in this model. CD47-expressing apoptotic cells and SIRPα+ macrophages were abundant in inflamed/rheumatic cardiac valves from both mice and humans. In vivo anti-CD47 blockade both prevented and treated valvular carditis in K/B.g7 mice. Blocking CD47 enhanced macrophage efferocytosis and reduced macrophage production of TNF and IL-6. These studies highlight the CD47:SIRPα interaction as a key driver of chronic cardiac valve inflammation and suggest these molecules as potential therapeutic targets to reduce cardiovascular disease risk in autoantibody-driven inflammatory diseases.","journal":"The Journal of Immunology","year":2022,"id":262178,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":917480,"name":"Jessica L. Faragher","orcid":"0000-0001-7593-3524","position":1,"is_corresponding":false},{"id":917481,"name":"Victoria Osinski","orcid":"0000-0002-8969-8454","position":2,"is_corresponding":false},{"id":917982,"name":"Jennifer L. Auger","orcid":null,"position":3,"is_corresponding":false},{"id":512196,"name":"Rochus K. Voeller","orcid":"0009-0005-8077-8916","position":4,"is_corresponding":false},{"id":917482,"name":"Aubyn Marath","orcid":"0000-0003-2300-1674","position":5,"is_corresponding":false},{"id":470890,"name":"Bryce A. Binstadt","orcid":"0000-0003-3127-3856","position":6,"is_corresponding":false},{"id":917479,"name":"Lee A. Meier","orcid":"0000-0002-6334-1633","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T00:26:20.717229Z","pmid":"35867674","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":[]}