{"doi":"10.17615/r24d-qd46","title":"MerTK is required for apoptotic cell–induced T cell tolerance","abstract":"Self-antigens expressed by apoptotic cells (ACs) may become targets for autoimmunity. Tolerance to these antigens is partly established by an ill-defined capacity of ACs to inhibit antigen-presenting cells such as dendritic cells (DCs). We present evidence that the receptor tyrosine kinase Mer (MerTK) has a key role in mediating AC-induced inhibition of DC activation/maturation. Pretreatment of DCs prepared from nonobese diabetic (NOD) mice with AC blocked secretion of proinflammatory cytokines, up-regulation of costimulatory molecule expression, and T cell activation. The effect of ACs on DCs was dependent on Gas6, which is a MerTK ligand. NOD DCs lacking MerTK expression (NOD.MerTKKD/KD) were resistant to AC-induced inhibition. Notably, autoimmune diabetes was exacerbated in NOD.MerTKKD/KD versus NOD mice expressing the transgenic BDC T cell receptor. In addition, β cell–specific CD4+ T cells adoptively transferred into NOD.MerTKKD/KD mice in which β cell apoptosis was induced with streptozotocin exhibited increased expansion and differentiation into type 1 T cell effectors. In both models, the lack of MerTK expression was associated with an increased frequency of activated pancreatic CD11c+CD8α+ DCs, which exhibited an enhanced T cell stimulatory capacity. These findings demonstrate that MerTK plays a critical role in regulating self-tolerance mediated between ACs, DCs, and T cells.","journal":"UNC Libraries","year":2020,"id":137870,"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":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":596193,"name":"Yaming Wang","orcid":"0000-0002-8208-8696","position":1,"is_corresponding":false},{"id":533176,"name":"Roland Tisch","orcid":"0000-0001-7751-7241","position":2,"is_corresponding":false},{"id":304429,"name":"H. Shelton Earp","orcid":"0000-0003-1229-4619","position":3,"is_corresponding":false},{"id":219937,"name":"Glenn K. Matsushima","orcid":null,"position":4,"is_corresponding":false},{"id":599203,"name":"Yingsu Huang","orcid":null,"position":5,"is_corresponding":false},{"id":436391,"name":"Pradip Sen","orcid":"0000-0003-1712-5312","position":6,"is_corresponding":false},{"id":598558,"name":"Rafael R. Flores","orcid":"0000-0002-5580-6381","position":7,"is_corresponding":false},{"id":598559,"name":"Zuoan Yi","orcid":"0000-0003-3130-7323","position":8,"is_corresponding":false},{"id":530709,"name":"Mark A. Wallet","orcid":"0000-0003-0802-9548","position":9,"is_corresponding":false},{"id":598560,"name":"Bo Wang","orcid":"0000-0003-0733-3599","position":10,"is_corresponding":false},{"id":389036,"name":"Clayton E. Mathews","orcid":"0000-0002-8817-6355","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:59.449905Z","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":[]}