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However, the role of CD4\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T cells on LTS pathogenesis. In this study, human LTS specimens revealed a higher population of CD4\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    cells reduced Th17 cells and attenuated fibrosis, demonstrating CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells\u2019 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\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.158456","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T12:39:41Z","timestamp":1683635981000},"source":"Crossref","is-referenced-by-count":29,"title":["Sirolimus-eluting airway stent reduces profibrotic Th17 cells and inhibits laryngotracheal stenosis"],"prefix":"10.1172","volume":"8","author":[{"given":"Kevin M.","family":"Motz","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8619-7312","authenticated-orcid":true,"given":"Ioan A.","family":"Lina","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Johns Hopkins School of Medicine, 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