{"doi":"10.1073/pnas.2409563122","title":"Local control of T cell fate in lymph nodes safely and durably reverses myelin-driven autoimmunity","abstract":"Development of tolerogenic, antigen-specific immunotherapies could overcome limitations of existing treatments for inflammatory autoimmune diseases by achieving potent, durable remission without impacting healthy immune surveillance. Here, we deliver diffusion-limited polymer depots to lymph nodes to locally guide T cell fates for the treatment of multiple sclerosis (MS), an autoimmune disease that occurs when the immune system mistakenly attacks myelin. In preclinical MS models, depots loaded with myelin self-antigen and tolerizing cues mediate localized retention of activated CD4 T cells, promote myelin-specific regulatory T cells, and reshape inflammation in the central nervous system (CNS) to eliminate lesions. Selective disease reversal is achieved with a single treatment that induces long-lasting remission without hindering healthy responses to vaccine challenge with foreign antigen. Furthermore, depots offer favorable chemistry and manufacturing control features and are well tolerated in non-human primates. This work supports a clinically feasible concept for inducing safe, effective, antigen-specific tolerance without systemic or repeated dosing.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":524770,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"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":776368,"name":"Emily A. Gosselin","orcid":"0000-0002-1177-0153","position":1,"is_corresponding":false},{"id":733393,"name":"Shannon J. Tsai","orcid":null,"position":2,"is_corresponding":false},{"id":342820,"name":"Robert S. Oakes","orcid":"0000-0003-3783-6488","position":3,"is_corresponding":false},{"id":672261,"name":"Zahra Habibabady","orcid":"0000-0002-3314-3716","position":4,"is_corresponding":false},{"id":708884,"name":"Marian A. Ackun‐Farmmer","orcid":"0000-0003-3081-5115","position":5,"is_corresponding":false},{"id":332671,"name":"Sean T. Carey","orcid":"0000-0003-1851-0300","position":6,"is_corresponding":false},{"id":892077,"name":"Shrey Shah","orcid":"0000-0001-7037-6845","position":7,"is_corresponding":false},{"id":846240,"name":"Ruochen Shen","orcid":"0000-0001-9967-4758","position":8,"is_corresponding":false},{"id":333341,"name":"Eugene Froimchuk","orcid":null,"position":9,"is_corresponding":false},{"id":909165,"name":"Haleigh B. Eppler","orcid":"0000-0001-6332-3331","position":10,"is_corresponding":false},{"id":1055277,"name":"Christopher J. Bridgeman","orcid":"0009-0009-6771-5266","position":11,"is_corresponding":false},{"id":739032,"name":"Alexis A. Yanes","orcid":null,"position":12,"is_corresponding":false},{"id":1302438,"name":"Ryan A. McIlvaine","orcid":"0000-0002-6115-1350","position":13,"is_corresponding":false},{"id":776808,"name":"Maeesha Noshin","orcid":null,"position":14,"is_corresponding":false},{"id":106717,"name":"Lisa H. Tostanoski","orcid":"0000-0001-9255-5684","position":15,"is_corresponding":false},{"id":728569,"name":"Sheneil K. Black","orcid":"0009-0000-9208-7534","position":16,"is_corresponding":false},{"id":729245,"name":"Xiangbin Zeng","orcid":null,"position":17,"is_corresponding":false},{"id":598366,"name":"Agnes M. Azimzadeh","orcid":"0000-0003-0761-6353","position":18,"is_corresponding":false},{"id":471569,"name":"Richard N. Pierson","orcid":"0000-0003-3764-4590","position":19,"is_corresponding":false},{"id":108992,"name":"Jonathan S. Bromberg","orcid":"0000-0002-1407-8795","position":20,"is_corresponding":false},{"id":232584,"name":"Christopher M. Jewell","orcid":"0000-0002-6668-6928","position":21,"is_corresponding":false},{"id":378030,"name":"Senta M. Kapnick","orcid":"0000-0002-2246-7053","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:50:16.562292Z","pmid":"41183200","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":[]}