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However, immunization with soluble egg Ag in CFA markedly exacerbates the lesions by inducing a potent proinflammatory environment with high levels of IFN\u2010\u03b3 and IL\u201017, which are signature cytokines of distinct Th1\u2010 <jats:italic>versus<\/jats:italic> Th17\u2010cell lineages. To determine the relative role of these subsets in disease exacerbation, we examined mice deficient in T\u2010bet (T\u2010bet<jats:sup>\u2212\/\u2212<\/jats:sup>), which is required for Th1 differentiation and IFN\u2010\u03b3 production. We now report that immunization with soluble egg Ag in CFA caused a significantly greater enhancement of egg\u2010induced hepatic immunopathology in T\u2010bet<jats:sup>\u2212\/\u2212<\/jats:sup> mice compared with WT controls, and analysis of their granulomas disclosed a higher proportion of activated DC and CD4<jats:sup>+<\/jats:sup> T cells, as well as a marked influx of neutrophils. The absence of IFN\u2010\u03b3 in the T\u2010bet<jats:sup>\u2212\/\u2212<\/jats:sup> mice correlated with a marked increase in IL\u201023p19, IL\u201017 and TNF\u2010\u03b1 in granulomas and MLN. In contrast, T\u2010bet<jats:sup>\u2212\/\u2212<\/jats:sup> mice had lower levels of IL\u20104, IL\u20105 and IL\u201010 and a reduction in FIZZ1 and FoxP3 expression, suggesting diminished regulatory activity, respectively, by alternatively activated macrophages and Treg. These findings demonstrate that T\u2010bet\u2010dependent signaling negatively regulates Th17\u2010mediated immunopathology in severe schistosomiasis.<\/jats:p>","DOI":"10.1002\/eji.200939325","type":"journal-article","created":{"date-parts":[[2009,8,27]],"date-time":"2009-08-27T17:11:49Z","timestamp":1251393109000},"page":"2470-2481","source":"Crossref","is-referenced-by-count":41,"title":["T\u2010bet protects against exacerbation of schistosome egg\u2010induced immunopathology by regulating Th17\u2010mediated inflammation"],"prefix":"10.1002","volume":"39","author":[{"given":"Laura I.","family":"Rutitzky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel 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