{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:28:33Z","timestamp":1791275313292,"version":"4.1.0"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2004,9,1]],"date-time":"2004-09-01T00:00:00Z","timestamp":1093996800000},"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":[[2004,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fibrosis is a characteristic feature in the pathogenesis of a wide spectrum of diseases. Recently, it was suggested that IL-13-dependent fibrosis develops through a TGF-\u03b21 and matrix metalloproteinase-9-dependent (MMP-9) mechanism. However, the significance of this pathway in a natural disorder of fibrosis was not investigated. In this study, we examined the role of TGF-\u03b2 in IL-13-dependent liver fibrosis caused by Schistosoma mansoni infection. Infected IL-13\u2212\/\u2212 mice showed an almost complete abrogation of fibrosis despite continued and undiminished production of TGF-\u03b21. Although MMP-9 activity was implicated in the IL-13 pathway, MMP-9\u2212\/\u2212 mice displayed no reduction in fibrosis, even when chronically infected. To directly test the requirement for TGF-\u03b2, studies were also performed with neutralizing anti-TGF-\u03b2 Abs, soluble antagonists (soluble TGF-\u03b2R-Fc), and Tg mice (Smad3\u2212\/\u2212 and TGF-\u03b2RII-Fc Tg) that have disruptions in all or part of the TGF-\u03b2 signaling cascade. In all cases, fibrosis developed normally and with kinetics similar to wild-type mice. Production of IL-13 was also unaffected. Finally, several genes, including interstitial collagens, several MMPs, and tissue inhibitors of metalloprotease-1 were up-regulated in TGF-\u03b21\u2212\/\u2212 mice by IL-13, demonstrating that IL-13 activates the fibrogenic machinery directly. Together, these studies provide unequivocal evidence of a pathway of fibrogenesis that is IL-13 dependent but TGF-\u03b21 independent, illustrating the importance of targeting IL-13 directly in the treatment of infection-induced fibrosis.<\/jats:p>","DOI":"10.4049\/jimmunol.173.6.4020","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:57:29Z","timestamp":1398034649000},"page":"4020-4029","source":"Crossref","is-referenced-by-count":332,"title":["IL-13 Activates a Mechanism of Tissue Fibrosis That Is Completely TGF-\u03b2 Independent"],"prefix":"10.1093","volume":"173","author":[{"given":"Mallika","family":"Kaviratne","sequence":"first","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hesse","sequence":"additional","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Leusink","sequence":"additional","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen W","family":"Cheever","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute , Rockville, MD 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Davies","sequence":"additional","affiliation":[{"name":"Tropical Disease Research Unit, Department of Pathology, Veterans Affairs Medical Center , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H","family":"McKerrow","sequence":"additional","affiliation":[{"name":"Tropical Disease Research Unit, Department of Pathology, Veterans Affairs Medical Center , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalage M","family":"Wakefield","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"Letterio","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Wynn","sequence":"additional","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,9,15]]},"reference":[{"key":"2025032617340106700_R1","first-page":"787","volume-title":"Nature","year":"1996"},{"key":"2025032617340106700_R2","first-page":"48","volume-title":"Curr. 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