{"doi":"10.1101/2025.07.24.665398","title":"Regulatory T cells epigenetically reprogrammed from autoreactive effector T cells mitigate established autoimmunity","abstract":"Abstract Reprogramming autoreactive CD4 + effector T (T eff ) cells into immunosuppressive regulatory T (T reg ) cells represents a promising strategy for treating established autoimmune diseases. However, the stability and function of such reprogrammed T regs under inflammatory conditions remain unclear. Here, we show that demethylation of core T reg identity genes in T eff cells yields lineage-stable Effector T cell Reprogrammed T regs (ER-T regs ). A single adoptive transfer of ER-T regs not only prevents autoimmune neuroinflammation in mice when given before disease onset but also arrests its progression when administered after onset. Compared to Foxp3-overexpressing T eff cells, induced T regs from naïve precursors, and endogenous T regs , ER-T regs provide superior protection against autoimmune neuroinflammation. This enhanced efficacy stems from their inherited autoantigen specificity and selectively preserved effector-cell transcriptional programs, which together bolster their fitness in inflammatory environments and enhance their suppressive capacity. Our results establish epigenetic reprogramming of autoreactive T eff cells as an effective approach to generate potent, stable T regs for the treatment of refractory autoimmune conditions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":571033,"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":0.939,"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":868979,"name":"James Cameron","orcid":"0000-0002-0772-0292","position":1,"is_corresponding":false},{"id":388580,"name":"Hayley I. Muendlein","orcid":"0000-0003-3006-5780","position":2,"is_corresponding":false},{"id":1208462,"name":"Mei-An Nolan","orcid":"0000-0002-8109-7339","position":3,"is_corresponding":false},{"id":1371054,"name":"Jamie L. Leiriao","orcid":"0000-0001-9215-3351","position":4,"is_corresponding":false},{"id":700472,"name":"James H. Kim","orcid":"0000-0002-8311-5000","position":5,"is_corresponding":false},{"id":51936,"name":"Alexander Poltorak","orcid":"0000-0002-5375-6587","position":6,"is_corresponding":false},{"id":422348,"name":"Xudong Li","orcid":"0000-0002-2688-740X","position":7,"is_corresponding":false},{"id":1437068,"name":"Tyler R. Colson","orcid":"0000-0001-7124-2208","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:11.713851Z","pmid":"40766652","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":[]}