{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:22:06Z","timestamp":1785428526453,"version":"3.56.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Endogenous IL-15 deficiency promotes lung fibrosis; therefore, we examined the effect of induced IL-15 in restricting the progression of lung fibrosis. Our objective in this work was to establish a novel therapeutic molecule for pulmonary fibrosis. Western blot, qPCR, and ELISA were performed on the lung tissues of IL-15\u2013deficient mice, and recombinant IL-15 (rIL-15)\u2013treated CC10\u2013IL-13 and CC10\u2013TGF-\u03b1 mice, and allergen-challenged CC10\u2013IL-15 mice were examined to establish the antifibrotic effect of IL-15 in lung fibrosis. We show that endogenous IL-15 deficiency induces baseline profibrotic cytokine and collagen accumulation in the lung, and pharmacological delivery of rIL-15 downregulates Aspergillus antigen\u2013induced lung collagen, the profibrotic cytokines IL-13 and TGF-\u03b21, and \u03b1-SMA+ and FSP1+ cells in mice. To confirm that overexpression of IL-15 diminishes pulmonary fibrosis, we generated CC10-rtTA-tetO7\u2013IL-15 transgenic mice and challenged them with Aspergillus antigen. Aspergillus antigen\u2013challenged, doxycycline (DOX)-treated CC10\u2013IL-15 transgenic mice exhibited decreased collagen accumulation, profibrotic cytokine (IL-13 and TGF-\u03b21) expression, and \u03b1-SMA+ and FSP1+ cells compared with IL-15\u2013overexpressing mice not treated with DOX. Additionally, to establish that the antifibrotic effect of IL-15 is not limited to allergen-induced fibrosis, we showed that rIL-15 or IL-15 agonist treatment restricted pulmonary fibrosis even in CC10\u2013IL-13 and CC10\u2013TGF-\u03b1 mice. Mechanistically, we show that T-helper cell type 17 suppressor IL-15\u2013responsive ROR\u03b3+ T regulatory cells are induced in DOX-treated, allergen-challenged IL-15\u2013overexpressing mice, which may be a novel pathway for restricting progression of pulmonary fibrosis. Taken together, our data establishes antifibrotic activity of IL-15 that might be a novel therapeutic molecule to combat the development of pulmonary fibrosis.<\/jats:p>","DOI":"10.1165\/rcmb.2018-0254oc","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T16:38:26Z","timestamp":1548952706000},"page":"97-109","source":"Crossref","is-referenced-by-count":23,"title":["Attenuation of Allergen-, IL-13\u2013, and TGF-\u03b1\u2013induced Lung Fibrosis after the Treatment of rIL-15 in Mice"],"prefix":"10.1093","volume":"61","author":[{"given":"Sathisha","family":"Upparahalli Venkateshaiah","sequence":"first","affiliation":[{"name":"Section of Pulmonary Medicine, Department of Medicine, Tulane Eosinophilic Disorder Center, New Orleans, Louisiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rituraj","family":"Niranjan","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research, Vector Control Research Centre, Puducherry, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5470-6426","authenticated-orcid":false,"given":"Murli","family":"Manohar","sequence":"additional","affiliation":[{"name":"Section of Pulmonary Medicine, Department of Medicine, Tulane Eosinophilic Disorder Center, New Orleans, Louisiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alok K.","family":"Verma","sequence":"additional","affiliation":[{"name":"Section of Pulmonary Medicine, Department of Medicine, Tulane Eosinophilic Disorder Center, New Orleans, Louisiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemanth K.","family":"Kandikattu","sequence":"additional","affiliation":[{"name":"Section of Pulmonary Medicine, Department of Medicine, Tulane Eosinophilic Disorder Center, New Orleans, Louisiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph 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