{"doi":"10.1172/jci131799","title":"Haploidentical mixed chimerism cures autoimmunity in established type 1 diabetic mice","abstract":"Clinical trials are currently testing whether induction of haploidentical mixed chimerism (Haplo-MC) induces organ transplantation tolerance. Whether Haplo-MC can be used to treat established autoimmune diseases remains unknown. Here, we show that established autoimmunity in euthymic and adult-thymectomized NOD (H-2g7) mice was cured by induction of Haplo-MC under a non-myeloablative anti-thymocyte globulin-based conditioning regimen and infusion of CD4+ T cell-depleted hematopoietic graft from H-2b/g7 F1 donors that expressed autoimmune-resistant H-2b or from H-2s/g7 F1 donors that expressed autoimmune-susceptible H-2s. The cure was associated with enhanced thymic negative selection, increased thymic Treg (tTreg) production, and anergy or exhaustion of residual host-type autoreactive T cells in the periphery. The peripheral tolerance was accompanied by expansion of donor- and host-type CD62L-Helios+ tTregs as well as host-type Helios-Nrp1+ peripheral Tregs (pTregs) and PD-L1hi plasmacytoid DCs (pDCs). Depletion of donor- or host-type Tregs led to reduction of host-type PD-L1hi pDCs and recurrence of autoimmunity, whereas PD-L1 deficiency in host-type DCs led to reduction of host-type pDCs and Helios-Nrp1+ pTregs. Thus, induction of Haplo-MC reestablished both central and peripheral tolerance through mechanisms that depend on allo-MHC+ donor-type DCs, PD-L1hi host-type DCs, and the generation and persistence of donor- and host-type tTregs and pTregs.","journal":"Journal of Clinical Investigation","year":2020,"id":110087,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":524227,"name":"Xiaoqi Wang","orcid":"0000-0001-8251-9102","position":1,"is_corresponding":false},{"id":475917,"name":"Yongping Zhu","orcid":null,"position":2,"is_corresponding":false},{"id":524228,"name":"Mingfeng Zhang","orcid":"0000-0002-0138-3934","position":3,"is_corresponding":false},{"id":475918,"name":"Ubaydah Nasri","orcid":null,"position":4,"is_corresponding":false},{"id":524838,"name":"Sharne S. Sun","orcid":null,"position":5,"is_corresponding":false},{"id":249979,"name":"Stephen J. Forman","orcid":"0000-0002-2803-4152","position":6,"is_corresponding":false},{"id":283022,"name":"Arthur D. Riggs","orcid":"0000-0002-8184-5288","position":7,"is_corresponding":false},{"id":506457,"name":"Xi Zhang","orcid":"0000-0002-8548-2832","position":8,"is_corresponding":false},{"id":474662,"name":"Defu Zeng","orcid":"0000-0001-9585-1411","position":9,"is_corresponding":false},{"id":524226,"name":"Yuqing Liu","orcid":"0000-0002-6324-1296","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T23:12:54.309019Z","pmid":"32817590","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":[]}