{"doi":"10.3389/fimmu.2023.1248027","title":"Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells","abstract":"Introduction Ischemia reperfusion injury (IRI) confers worsened outcomes and is an increasing clinical problem in solid organ transplantation. Previously, we identified a “Ptch Hi ” T-cell subset that selectively received costimulatory signals from endothelial cell-derived Hedgehog (Hh) morphogens to mediate IRI-induced vascular inflammation. Methods Here, we used multi-omics approaches and developed a humanized mouse model to resolve functional and migratory heterogeneity within the PtchHi population. Results Hh-mediated costimulation induced oligoclonal and polyclonal expansion of clones within the PtchHi population, and we visualized three distinct subsets within inflamed, IRI-treated human skin xenografts exhibiting polyfunctional cytokine responses. One of these PtchHi subsets displayed features resembling recently described T peripheral helper cells, including elaboration of IFN-y and IL-21, expression of ICOS and PD-1, and upregulation of positioning molecules conferring recruitment and retention within peripheral but not lymphoid tissues. Ptch Hi T cells selectively homed to IRI-treated human skin xenografts to cause accelerated allograft loss, and Hh signaling was sufficient for this process to occur. Discussion Our studies define functional heterogeneity among a Ptch Hi T-cell population implicated in IRI.","journal":"Frontiers in Immunology","year":2023,"id":386873,"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":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":913386,"name":"Guiyu Song","orcid":"0000-0003-2617-9857","position":1,"is_corresponding":false},{"id":913964,"name":"Mahsa Nouri Barkestani","orcid":null,"position":2,"is_corresponding":false},{"id":248224,"name":"Zuzana Tobiásová","orcid":null,"position":3,"is_corresponding":false},{"id":1121426,"name":"Qianxun Wang","orcid":"0000-0001-9196-7505","position":4,"is_corresponding":false},{"id":663338,"name":"Quan Jiang","orcid":"0000-0001-8201-6417","position":5,"is_corresponding":false},{"id":1155717,"name":"Roberto Lopez","orcid":null,"position":6,"is_corresponding":false},{"id":1155718,"name":"Yasmin Adelekan-Kamara","orcid":null,"position":7,"is_corresponding":false},{"id":913387,"name":"Matthew Fan","orcid":"0000-0002-4042-6685","position":8,"is_corresponding":false},{"id":243205,"name":"Jordan S. Pober","orcid":"0000-0001-5990-1071","position":9,"is_corresponding":false},{"id":245131,"name":"George Tellides","orcid":"0000-0001-7042-8190","position":10,"is_corresponding":false},{"id":243204,"name":"Dan Jane‐wit","orcid":"0000-0001-7115-0362","position":11,"is_corresponding":false},{"id":304955,"name":"Shaoxun Wang","orcid":"0000-0002-1439-021X","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:18:00.717763Z","pmid":"37915586","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":[]}