ArticleJCI insight2023
Sirolimus-eluting airway stent reduces profibrotic Th17 cells and inhibits laryngotracheal stenosis.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Exploring pathogenetic mechanisms in subglottic stenosis: A narrative review toward an integrated molecular classification.Multidisciplinary respiratory medicine · 2026Article
- M6A demethylase ALKBH5 mediated Igfbp4 mRNA m6A modification drives fibroblast activation and pathological upper airway fibrosis.Clinical and translational medicine · 2026Article
- Integrating mechanical cues inFrontiers in immunology · 2026Review
- Nanomedicine-Driven Precision Therapy for Renal Fibrosis: From Mechanistic Insights to Kidney-Targeted Interventions.International journal of nanomedicine · 2026Review
- The evolution of airway stenting research: a bibliometric analysis of the 100 most influential articles.Journal of thoracic disease · 2025Article
- The benefit and effectiveness of biodegradable drug-coated stents in treating refractory pediatric laryngotracheal stenosis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Article
- Identification of the role ofJournal of thoracic disease · 2025Article
- Preclinical Vocal Fold and Airway Injury Models: A Scoping Review.Laryngoscope investigative otolaryngology · 2025Review
- Crosstalk Between Th17 Cells and Renal Tubular Epithelial Cells Promotes Fibrotic Progression in IgA Nephropathy.Current medical science · 2025Article
- Localized Knockout of E-Cadherin in Subglottic Mucosa Increases Fibrosis.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025Article
- Dynamic single-cell transcriptomic reveals the cellular heterogeneity and a novel fibroblast subpopulation in laryngotracheal stenosis.Biology direct · 2025Article
- Polytrauma impairs fracture healing accompanied by increased persistence of innate inflammatory stimuli and reduced adaptive response.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
- Review
- Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway.Nature communications · 2025Article
- Advances in studies on tracheal stent design addressing the related complications.Materials today. Bio · 2024Review
- Oral Everolimus Following Dilation in Idiopathic Subglottic Stenosis: A Phase 1 Nonrandomized Clinical Trial.JAMA otolaryngology-- head & neck surgery · 2024Article
- An Ovine Model Yields Histology and Gene Expression Changes Consistent with Laryngotracheal Stenosis.The Laryngoscope · 2024Article
- Drug-eluting stents from cardiology to pneumonology.Future cardiology · 2024Article
- Mesenchymal stem cells delivered via a bioactive disordered peptide-hydrogel platform modulate early inflammation and enhance skeletal repair in a polytrauma model.Journal of tissue engineeringArticle
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.