{"doi":"10.1093/jimmun/vkaf283.985","title":"STING and IFNalpha/beta receptor are required for antigen-specific apoptotic cell-induced peripheral tolerance 3152","abstract":"Abstract Description Autoreactive T cell infiltration, tissue destruction, and spread epitope-specific T cell activation underly CD4+ T cell-mediated autoimmune disease pathogenesis. Antigen (Ag)-containing biodegradable poly(lactide-co-glycolide) nanoparticle, i.e. tolerogenic immune-modifying particles/Cour Nanoparticles (TIMP/CNPs), treatment is both safe and efficacious for Ag-specific tolerance induction in mice and a Phase I/IIa clinical trial for celiac disease. Here, we identify that novel pathways are required for Ag-specific CNP-induced tolerance. The data show that myeloid cells phagocytose CNPs, undergo apoptosis, and release oxidized DNA (8-OHG). Subsequently, Ag-specific CNP treatment increases FoxP3+ and IL-10+ regulatory T cells via a stimulator of interferon genes (STING)/IFN-alpha/beta receptor (IFNAR)-dependent pathway. Treatment also regulates T cells specific for the spread epitopes associated with disease progression. Furthermore, induction of apoptosis via ECDI fixation, UV irradiation, X-ray irradiation, or culture of ECDI fixed RBCs with myeloid cells induces 8-OHG expression. Treatment of mice with these apoptotic cells, or Ag-coupled RBCs induces tolerance to the associated Ag and requires the host expression of STING/IFNAR pathways. Taken together, these results are the first to show that Ag-specific tolerance induced by the presence of apoptotic cells and by CNP-induced apoptosis requires the STING/IFNAR pathway. Funding Sources This work was supported by grants to S.D.M. from Cour Pharmaceutical Development Company, NIH grant R01AI148076; and by gifts from the Johnnie Walkers MS Foundation, the Amy and David Fulton Foundation, the Crammer Family Foundation, the Thomas and Deige McLaughlin Foundation, and the Rottering Family Foundation. Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)","journal":"The Journal of Immunology","year":2025,"id":582640,"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":0.9542,"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":449606,"name":"Andrew C. Cogswell","orcid":"0000-0002-6951-6713","position":1,"is_corresponding":false},{"id":741876,"name":"Tobias Neef","orcid":"0000-0002-8256-1455","position":2,"is_corresponding":false},{"id":915298,"name":"Ming-Yi Chiang","orcid":"0000-0003-0959-2439","position":3,"is_corresponding":false},{"id":1495020,"name":"Derrick McCarthy","orcid":null,"position":4,"is_corresponding":false},{"id":625496,"name":"Adam Elhofy","orcid":"0000-0002-3060-7829","position":5,"is_corresponding":false},{"id":1495021,"name":"Mairah T. Khan","orcid":null,"position":6,"is_corresponding":false},{"id":242016,"name":"Joshua J. Meeks","orcid":"0000-0002-5444-5510","position":7,"is_corresponding":false},{"id":242015,"name":"Stephen D. Miller","orcid":"0000-0002-9556-0718","position":8,"is_corresponding":false},{"id":260784,"name":"Joseph R. Podojil","orcid":"0000-0002-5818-8515","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":[]}