{"doi":"10.1172/jci.insight.158456","title":"Sirolimus-eluting airway stent reduces profibrotic Th17 cells and inhibits laryngotracheal stenosis","abstract":"Laryngotracheal stenosis (LTS) is pathologic fibrotic narrowing of the larynx and trachea characterized by hypermetabolic fibroblasts and CD4+ T cell-mediated inflammation. However, the role of CD4+ T cells in promoting LTS fibrosis is unknown. The mTOR signaling pathways have been shown to regulate the T cell phenotype. Here we investigated the influence of mTOR signaling in CD4+ T cells on LTS pathogenesis. In this study, human LTS specimens revealed a higher population of CD4+ T cells expressing the activated isoform of mTOR. In a murine LTS model, targeting mTOR with systemic sirolimus and a sirolimus-eluting airway stent reduced fibrosis and Th17 cells. Selective deletion of mTOR in CD4+ cells reduced Th17 cells and attenuated fibrosis, demonstrating CD4+ T cells' pathologic role in LTS. Multispectral immunofluorescence of human LTS revealed increased Th17 cells. In vitro, Th17 cells increased collagen-1 production by LTS fibroblasts, which was prevented with sirolimus pretreatment of Th17 cells. Collectively, mTOR signaling drove pathologic CD4+ T cell phenotypes in LTS, and targeting mTOR with sirolimus was effective at treating LTS through inhibition of profibrotic Th17 cells. Finally, sirolimus may be delivered locally with a drug-eluting stent, transforming clinical therapy for LTS.","journal":"JCI Insight","year":2023,"id":326884,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"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":381363,"name":"Ioan Lina","orcid":"0000-0002-8619-7312","position":1,"is_corresponding":false},{"id":765235,"name":"Idris Samad","orcid":null,"position":2,"is_corresponding":false},{"id":1046481,"name":"Michael K. Murphy","orcid":"0000-0002-0285-884X","position":3,"is_corresponding":false},{"id":1046482,"name":"Madhavi Duvvuri","orcid":"0000-0002-2883-5638","position":4,"is_corresponding":false},{"id":381362,"name":"Ruth J. Davis","orcid":"0000-0001-9592-932X","position":5,"is_corresponding":false},{"id":381368,"name":"Alexander Gelbard","orcid":"0000-0003-0078-1305","position":6,"is_corresponding":false},{"id":238247,"name":"Liam Chung","orcid":"0000-0002-3919-6253","position":7,"is_corresponding":false},{"id":229835,"name":"Yee Chan‐Li","orcid":null,"position":8,"is_corresponding":false},{"id":642564,"name":"Samuel L. Collins","orcid":"0000-0002-0292-6937","position":9,"is_corresponding":false},{"id":228375,"name":"Jonathan D. Powell","orcid":"0000-0002-0850-2852","position":10,"is_corresponding":false},{"id":237878,"name":"Jennifer H. Elisseeff","orcid":"0000-0002-5066-1996","position":11,"is_corresponding":false},{"id":228374,"name":"Maureen R. Horton","orcid":"0000-0002-0621-1015","position":12,"is_corresponding":false},{"id":240456,"name":"Alexander T. Hillel","orcid":"0000-0001-8471-5449","position":13,"is_corresponding":false},{"id":381366,"name":"Kevin Motz","orcid":"0000-0002-9255-7265","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:08:37.840107Z","pmid":"37159282","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":[]}