{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:03:24Z","timestamp":1788851004038,"version":"build-2803163510"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08HL105536"],"award-info":[{"award-number":["K08HL105536"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01HL014985-41"],"award-info":[{"award-number":["P01HL014985-41"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R24HL123767"],"award-info":[{"award-number":["R24HL123767"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The etiology of schistosomiasis-associated pulmonary arterial hypertension (PAH), a major cause of PAH worldwide, is poorly understood. Schistosoma mansoni exposure results in prototypical type-2 inflammation. Furthermore, transforming growth factor (TGF)-\u03b2 signaling is required for experimental pulmonary hypertension (PH) caused by Schistosoma exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We hypothesized type-2 inflammation driven by IL-4 and IL-13 is necessary for Schistosoma-induced TGF-\u03b2\u2013dependent vascular remodeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Wild-type, IL-4\u2212\/\u2212, IL-13\u2212\/\u2212, and IL-4\u2212\/\u2212IL-13\u2212\/\u2212 mice (C57BL6\/J background) were intraperitoneally sensitized and intravenously challenged with S. mansoni eggs to induce experimental PH. Right ventricular catheterization was then performed, followed by quantitative analysis of the lung tissue. Lung tissue from patients with schistosomiasis-associated and connective tissue disease\u2013associated PAH was also systematically analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Mice with experimental Schistosoma-induced PH had evidence of increased IL-4 and IL-13 signaling. IL-4\u2212\/\u2212IL-13\u2212\/\u2212 mice, but not single knockout IL-4\u2212\/\u2212 or IL-13\u2212\/\u2212 mice, were protected from Schistosoma-induced PH, with decreased right ventricular pressures, pulmonary vascular remodeling, and right ventricular hypertrophy. IL-4\u2212\/\u2212IL-13\u2212\/\u2212 mice had less pulmonary vascular phospho\u2013signal transducer and activator of transcription 6 (STAT6) and phospho-Smad2\/3 activity, potentially caused by decreased TGF-\u03b2 activation by macrophages. In vivo treatment with a STAT6 inhibitor and IL-4\u2212\/\u2212IL-13\u2212\/\u2212 bone marrow transplantation also protected against Schistosoma-PH. Lung tissue from patients with schistosomiasis-associated and connective tissue disease\u2013associated PAH had evidence of type-2 inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Combined IL-4 and IL-13 deficiency is required for protection against TGF-\u03b2\u2013induced pulmonary vascular disease after Schistosoma exposure, and targeted inhibition of this pathway is a potential novel therapeutic approach for patients with schistosomiasis-associated PAH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201410-1820oc","type":"journal-article","created":{"date-parts":[[2015,7,20]],"date-time":"2015-07-20T16:44:45Z","timestamp":1437410685000},"page":"998-1008","source":"Crossref","is-referenced-by-count":93,"title":["The Causal Role of IL-4 and IL-13 in\n                    <i>Schistosoma mansoni<\/i>\n                    Pulmonary Hypertension"],"prefix":"10.1093","volume":"192","author":[{"given":"Rahul","family":"Kumar","sequence":"first","affiliation":[{"name":"Program in Translational Lung Research, Department of Medicine, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Mickael","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Department of Medicine, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Chabon","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Department of Medicine, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Gebreab","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Department of Medicine, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alleluiah","family":"Rutebemberwa","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Department of Medicine, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Rodriguez","family":"Garcia","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Department of Medicine, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Koyanagi","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Department of Medicine, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Sanders","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Department of Medicine, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Gandjeva","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Department of Medicine, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Kearns","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Barthel","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais","family":"Mauad","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sao Paulo University Medical School, Sao Paulo, Brazil; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Bandeira","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial S. 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