{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:50:18Z","timestamp":1790898618305,"version":"4.1.0"},"reference-count":73,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,3,17]]},"abstract":"<jats:p>Highly polarized type 2 cytokine responses can be harmful and even lethal to the host if they are too vigorous or persist too long. Therefore, it is important to elucidate the mechanisms that down-regulate these reactions. Interleukin (IL)-13 has emerged as a central mediator of T helper cell (Th)2-dominant immune responses, exhibiting a diverse array of functional activities including regulation of airway hyperreactivity, resistance to nematode parasites, and tissue remodeling and fibrosis. Here, we show that IL-13 receptor (R)\u03b12 is a critical down-regulatory factor of IL-13\u2013mediated tissue fibrosis induced by the parasitic helminth Schistosoma mansoni. IL-13R\u03b12 expression was induced after the onset of the fibrotic response, IL-10, IL-13, and Stat6 dependent, and inhibited by the Th1-inducing adjuvant IL-12. Strikingly, schistosome-infected C57BL\/6 and BALB\/c IL-13R\u03b12\u2013deficient mice showed a marked exacerbation in hepatic fibrosis, despite displaying no change in granuloma size, tissue eosinophilia, or mastocytosis. Fibrosis increased despite the fact that IL-13 levels decreased significantly in the liver and serum. Importantly, pathology was prevented when IL-13R\u03b12\u2013deficient mice were treated with a soluble IL-13R\u03b12-Fc construct, formally demonstrating that their exacerbated fibrotic response was due to heightened IL-13 activity. Together, these studies illustrate the central role played by the IL-13R\u03b12 in the down-regulation of a chronic and pathogenic Th2-mediated immune response.<\/jats:p>","DOI":"10.1084\/jem.20020903","type":"journal-article","created":{"date-parts":[[2003,3,17]],"date-time":"2003-03-17T15:02:51Z","timestamp":1047913371000},"page":"687-701","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":205,"title":["Regulation and Function of the Interleukin 13 Receptor \u03b1 2 During a T Helper Cell Type 2\u2013dominant Immune Response"],"prefix":"10.1084","volume":"197","author":[{"given":"Monica G.","family":"Chiaramonte","sequence":"first","affiliation":[{"name":"1Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Mentink-Kane","sequence":"additional","affiliation":[{"name":"1Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"2Wyeth-Genetics Institute, Cambridge, MA 01810"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen W.","family":"Cheever","sequence":"additional","affiliation":[{"name":"3Biomedical Research Institute, Rockville, MD 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Whitters","sequence":"additional","affiliation":[{"name":"2Wyeth-Genetics Institute, Cambridge, MA 01810"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.P.","family":"Goad","sequence":"additional","affiliation":[{"name":"2Wyeth-Genetics Institute, Cambridge, MA 01810"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Wong","sequence":"additional","affiliation":[{"name":"2Wyeth-Genetics Institute, Cambridge, MA 01810"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Collins","sequence":"additional","affiliation":[{"name":"2Wyeth-Genetics Institute, Cambridge, MA 01810"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra D.","family":"Donaldson","sequence":"additional","affiliation":[{"name":"2Wyeth-Genetics Institute, Cambridge, MA 01810"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Grusby","sequence":"additional","affiliation":[{"name":"4Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Wynn","sequence":"additional","affiliation":[{"name":"1Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2003,3,17]]},"reference":[{"key":"2023072512004440100_BIB1","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1378\/chest.117.4.1162","volume":"117","year":"2000","journal-title":"Chest."},{"key":"2023072512004440100_BIB2","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S0952-7915(99)80070-3","volume":"11","year":"1999","journal-title":"Curr. 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