{"doi":"10.3389/fimmu.2022.765319","title":"Targeting the Retinoid X Receptor Pathway Prevents and Ameliorates Murine Chronic Graft-Versus-Host Disease","abstract":"Most allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients receive peripheral blood stem cell grafts resulting in a 30%-70% incidence of chronic graft-versus-host disease (cGVHD), a major cause of mortality and morbidity in long-term survivors. While systemic steroids remain the standard of care for first-line therapy, patients may require long-term administration, and those with steroid-resistant or refractory cGVHD have a worse prognosis. Although durable and deep responses with second-line therapies can be achieved in some patients, there remains an urgent need for new therapies. In this study, we evaluated the efficacy of IRX4204, a novel agonist that activates RXRs and is in clinical trials for cancer treatment to prevent and treat cGVHD in two complementary murine models. In a major histocompatibility complex mismatched, non-sclerodermatous multiorgan system model with bronchiolitis obliterans, IRX4204 prevented and reversed cGVHD including associated pulmonary dysfunction with restoration of germinal center T-follicular helper: T-follicular regulatory cell balance. In a minor histocompatibility antigen disparate sclerodermatous model, IRX4204 treatment significantly prevented and ameliorated skin cGVHD by reducing Th1 and Th17 differentiation due to anti-inflammatory properties. Together, these results indicate that IRX4204 is a promising therapeutic option to treat cGVHD with bronchiolitis obliterans or sclerodermatous manifestations.","journal":"Frontiers in Immunology","year":2022,"id":292472,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":789824,"name":"Michael Zaiken","orcid":"0000-0001-6971-3170","position":1,"is_corresponding":false},{"id":707520,"name":"Fathima A. Mohamed","orcid":"0000-0003-4270-8560","position":2,"is_corresponding":false},{"id":790384,"name":"Ryan Flynn","orcid":null,"position":3,"is_corresponding":false},{"id":789823,"name":"Jing Du","orcid":"0000-0003-1350-2811","position":4,"is_corresponding":false},{"id":708177,"name":"Stephanie Y. Rhee","orcid":null,"position":5,"is_corresponding":false},{"id":886264,"name":"Megan Riddle","orcid":"0000-0002-9557-217X","position":6,"is_corresponding":false},{"id":262402,"name":"Ethan G. Aguilar","orcid":"0000-0002-3600-0913","position":7,"is_corresponding":false},{"id":488197,"name":"Angela Panoskaltsis‐Mortari","orcid":"0000-0003-1802-1785","position":8,"is_corresponding":false},{"id":372525,"name":"Martin E. Sanders","orcid":"0000-0002-0007-0338","position":9,"is_corresponding":false},{"id":52067,"name":"Bruce R. Blazar","orcid":"0000-0002-9608-9841","position":10,"is_corresponding":false},{"id":597280,"name":"Govindarajan Thangavelu","orcid":"0000-0003-3524-9570","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T00:30:46.209549Z","pmid":"35359939","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":[]}