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In C57BL\/6 mice, pronounced exacerbation of immunopathology induced by immunization with schistosome egg Ag in CFA (SEA\/CFA) substantially recapitulates the natural high pathology seen in CBA mice; both are associated with a significant elevation of Th17\u2010 and Th1\u2010cell\u2010derived proinflammatory cytokines. We now investigated the relative contribution of the effector cytokines IL\u201017 and IFN\u2010\u03b3 in pathology development of 7\u2009wk\u2010infected, SEA\/CFA\u2010immunized, IL\u201017<jats:sup>\u2212\/\u2212<\/jats:sup>, IFN\u2010\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup>, and IL\u201017\/IFN\u2010\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup> mice. In IL\u201017<jats:sup>\u2212\/\u2212<\/jats:sup> mice there was significant reduction of immunopathology despite increased levels of IFN\u2010\u03b3, whereas in IFN\u2010\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup> mice, markedly exacerbated immunopathology correlated with an increase in IL\u201017. In IL\u201017\/IFN\u2010\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup> mice, complete resistance to SEA\/CFA\u2010induced disease exacerbation was associated with a reduction in IL\u201023p19, IL\u20101\u03b2, CXCL1 and iNOS, and with an increase in IL\u20105, IL\u201010 and Relm\u03b1. IL\u201017 and IFN\u2010\u03b3 were derived from distinct CD4<jats:sup>+<\/jats:sup> T cells in which production of each cytokine was suppressed by the other. Our results indicate that severe immunopathology in murine schistosomiasis is mainly driven by IL\u201017 and regulated by IFN\u2010\u03b3; however, in the absence of IL\u201017, IFN\u2010\u03b3 is capable of exerting a limited, yet significant, pathogenic function.<\/jats:p>","DOI":"10.1002\/eji.201041327","type":"journal-article","created":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T09:57:31Z","timestamp":1307699851000},"page":"2677-2687","source":"Crossref","is-referenced-by-count":56,"title":["Exacerbated egg\u2010induced immunopathology in murine <i>Schistosoma mansoni<\/i> infection is primarily mediated by IL\u201017 and restrained by IFN\u2010\u03b3"],"prefix":"10.1002","volume":"41","author":[{"given":"Laura I.","family":"Rutitzky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel J.","family":"Stadecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,8,12]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri843"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00101-7"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1987.37.85"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/144.2.148"},{"key":"e_1_2_6_6_2","doi-asserted-by":"crossref","first-page":"594","DOI":"10.4049\/jimmunol.118.2.594","article-title":"Schistosomiasis in the congenitally athymic (nude) mouse. 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