{"doi":"10.1007/s00395-024-01089-3","title":"4E-BP3 deficiency impairs dendritic cell activation and CD4+ T cell differentiation and attenuates α-myosin-specific T cell-mediated myocarditis in mice","abstract":null,"journal":"Basic Research in Cardiology","year":2024,"id":673725,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":870995,"name":"Kazuko Tajiri","orcid":"0000-0002-9759-1008","position":1,"is_corresponding":false},{"id":1760237,"name":"Zixun Yuan","orcid":null,"position":2,"is_corresponding":false},{"id":1760239,"name":"Yoshiko Murakata","orcid":null,"position":3,"is_corresponding":false},{"id":1760242,"name":"Zonghu Song","orcid":null,"position":4,"is_corresponding":false},{"id":1008209,"name":"Seiya Mizuno","orcid":"0000-0002-6740-5817","position":5,"is_corresponding":false},{"id":1450727,"name":"Dongzhu Xu","orcid":"0000-0001-6507-1959","position":6,"is_corresponding":false},{"id":1605701,"name":"Nobuyuki Murakoshi","orcid":null,"position":7,"is_corresponding":false},{"id":1382678,"name":"Siqi Li","orcid":"0000-0003-2085-4938","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"4E-BP3 deficiency impairs dendritic cell activation and CD4+ T cell differentiation and attenuates α-myosin-specific T cell-mediated myocarditis in mice","abstract":"Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare but potentially fatal immune-related adverse event. Previously, we reported a case of ICI-associated myocarditis with elevated autoantibodies to 4E-binding protein 3 (4E-BP3). Recent studies have suggested that 4E-BP3 may play an important role in tumor development. However, its role in cardiac diseases including myocarditis is unknown. We investigated the role of 4E-BP3 in an autoimmune myocarditis mouse model. Myocarditis was induced in wild-type and 4E-BP3 knockout mice by immunization with murine α-myosin peptide. 4E-BP3 gene expression was upregulated in the heart of myocarditis mouse. We found that genetic deletion of 4E-BP3 attenuated myocardial inflammation, reduced fibrosis area, and improved cardiac function in myocarditis mice. Studies in bone marrow-chimeric mice demonstrated that immune cell-derived 4E-BP3 plays a pivotal role in the pathogenesis of myocarditis. Immune cell transfer experiments revealed that 4E-BP3 deficiency in dendritic cells and CD4<sup>+</sup> T cells decreased disease severity in recipient mice. Furthermore, dendritic cells that were deficient in 4E-BP3 exhibited a diminished capacity to produce IL-6 and IL-1β. Naive CD4<sup>+</sup> T cells lacking 4E-BP3 had a reduced ability to differentiate into T-helper (Th)1 and Th17 cells. These findings suggest that 4E-BP3 in dendritic cells and CD4<sup>+</sup> T cells may be critically involved in the pathogenesis of α-myosin-specific T cell-mediated myocarditis. Thus, 4E-BP3 could be a possible therapeutic target for myocarditis.","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39516410","pmcid":null,"openalex_id":"https://openalex.org/W4404209471","authors":[],"funders":[{"funder_name":"JSPS KAKENHI","grant_id":"20K08396","title":null},{"funder_name":"JSPS KAKENHI","grant_id":"22KJ0425","title":null},{"funder_name":"JSPS KAKENHI","grant_id":"22J20356","title":null},{"funder_name":"JSPS KAKENHI","grant_id":"23K07518","title":null},{"funder_name":"Japan Research Foundation for Clinical Pharmacology","grant_id":"","title":null}],"total_grants":5,"fwci":1.5776,"citation_percentile":0.86241643,"influential_citations":0,"citation_trend":[{"year":2025,"count":4},{"year":2026,"count":5}],"oa_status":"closed","license":"https://www.springernature.com/gp/researchers/text-and-data-mining","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s00395-024-01089-3.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s00395-024-01089-3/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s00395-024-01089-3","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39516410","host_type":"repository"}],"fields_of_study":["Cancer Immunotherapy and Biomarkers","CAR-T cell therapy research","Melanoma and MAPK Pathways","Animals","Myocarditis","Dendritic Cells","Mice, Knockout","CD4-Positive T-Lymphocytes","Disease Models, Animal","Cell Differentiation","Mice","Mice, Inbred C57BL","Autoimmune Diseases","Lymphocyte Activation","Cardiac Myosins","Male","Myocardium"],"mesh_terms":["Animals","Autoimmune Diseases","Cell Differentiation","Dendritic Cells","Disease Models, Animal","Lymphocyte Activation","Male","Mice, Inbred C57BL","Myocarditis","Myocardium","CD4-Positive T-Lymphocytes","Mice, Knockout","Cardiac Myosins","Ventricular Myosins","Mice"],"keywords":["Myosin","Myocarditis","Cell","Cellular differentiation","T cell","Cell biology","Medicine","Dendritic cell","Internal medicine","Immunology","Chemistry","Endocrinology","Biology","Immune system","Biochemistry","Experimental autoimmune myocarditis","eukaryotic translation initiation factor","Immune Checkpoint Inhibitor","Cardio-oncology","Onco-cardiology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T14:19:16.746911Z","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":[]}