{"doi":"10.1172/jci178960","title":"Treg activation during allograft tolerance induction requires mitochondrion-induced TGF-β1 in type 1 conventional dendritic cells","abstract":"The role of conventional type 1 DCs (cDC1s) in tolerance induction to solid organ allografts is unknown and important for strategies that seek to prolong allograft viability. Using a murine model deficient in cDC1s, we report cDC1s are required for donor antigen and costimulation blockade (DST + CoB) tolerance induction and survival of cardiac allografts. cDC1 deficiency led to decreases in CD4+CD25+FoxP3+ T cells within allograft and spleen tissue of transplant recipients, and this was found to be antigen specific. Donor antigen stimulation induced TGF-β1 expression in both in vivo cDC1s and in vitro Flt3L-derived cDC1s. Genetic deletion of TGF-β1 in cDC1s prevented induction of antigen-specific CD4+CD25+FoxP3+ T cells and was associated with cardiac allograft rejection. In parallel, single-cell RNA sequencing and metabolic analysis revealed upregulation of cDC1 mitochondrial metabolic signatures after in vivo exposure to DST + CoB. Genetic inactivation of cDC1 mitochondrial metabolism reduced expression of cDC1 TGF-β1, decreased antigen-specific Treg populations, and impaired allograft tolerance. Taken together, our findings implicate cDC1s in strategies to preserve solid organ allografts and also implicate mitochondrial metabolism of cDC1s as a molecular mechanism to enhance the generation of antigen-specific CD4+CD25+FoxP3+ T cells through TGF-β1.","journal":"Journal of Clinical Investigation","year":2025,"id":518580,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"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":489832,"name":"Lei Zhang","orcid":"0000-0002-2227-0613","position":1,"is_corresponding":false},{"id":1069808,"name":"Rebecca Jones","orcid":"0000-0002-0970-1968","position":2,"is_corresponding":false},{"id":442255,"name":"Kristofor Glinton","orcid":"0000-0001-9301-7132","position":3,"is_corresponding":false},{"id":646489,"name":"Nikita Mani","orcid":"0000-0003-4688-7770","position":4,"is_corresponding":false},{"id":1304004,"name":"Hiroyasu Inui","orcid":null,"position":5,"is_corresponding":false},{"id":806833,"name":"Jesse T. Davidson","orcid":"0000-0003-1099-8444","position":6,"is_corresponding":false},{"id":230870,"name":"Samuel E. Weinberg","orcid":"0000-0002-9532-7051","position":7,"is_corresponding":false},{"id":104272,"name":"Navdeep S. Chandel","orcid":"0000-0001-7208-3886","position":8,"is_corresponding":false},{"id":92114,"name":"Maria‐Luisa Alegre","orcid":"0000-0001-5707-6194","position":9,"is_corresponding":false},{"id":238277,"name":"Edward B. Thorp","orcid":"0000-0003-1387-7058","position":10,"is_corresponding":false},{"id":418298,"name":"Samantha L. Schroth","orcid":"0000-0002-9764-5504","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:09.679930Z","pmid":"40644411","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":[]}