{"doi":"10.3389/frtra.2025.1612523","title":"Hypomethylating therapy mitigates acute allograft rejection in a murine lung transplant model","abstract":"Introduction: Acute cellular rejection of transplanted lung allografts involves activated cytotoxic T cells and reduced Regulatory T (Treg) cell function. Calcineurin inhibitors, the cornerstone of immunosuppressive regimens, suppress T cell cytotoxicity but inhibit Treg proliferation. The DNA hypomethylating agent decitabine (DAC) can abrogate T cell cytotoxicity while stimulating Treg proliferation. Methods: We sought to determine the effects of DAC treatment in a murine MHC-mismatched orthotopic lung transplant model. Results: Rescue treatment with DAC maintains lung allograft gross and histologic integrity with a reduction in cytotoxic T cell responses. CD4+FoxP3+ T cell depletion in Foxp3DTR mice exacerbated rejection lung injury compared to CD4+FoxP3+ T cell sufficient mice and failed to abolish the protective effect of DAC in this model. The protective effect of DAC was associated with a reduction in cytokine production from host T-cells. Discussion: Decitabine could offer a new line of treatment for acute lung allograft rejection, in part via its effects on Tregs.","journal":"Frontiers in Transplantation","year":2025,"id":553251,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"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":1320007,"name":"W.N. Daccarett-Bojanini","orcid":null,"position":1,"is_corresponding":false},{"id":271949,"name":"A.F. Villabona-Rueda","orcid":"0000-0002-6529-7162","position":2,"is_corresponding":false},{"id":1450282,"name":"Manuel Sollmann","orcid":null,"position":3,"is_corresponding":false},{"id":525241,"name":"Franco R. D’Alessio","orcid":"0000-0002-3728-0064","position":4,"is_corresponding":false},{"id":975790,"name":"Jeffrey M. Dodd‐o","orcid":"0000-0001-8895-210X","position":5,"is_corresponding":false},{"id":1449927,"name":"Kristine Yarnoff","orcid":"0000-0002-3442-8326","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:54:41.819682Z","pmid":"40626170","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":[]}