| First Author | Rutitzky LI | Year | 2009 |
| Journal | Eur J Immunol | Volume | 39 |
| Issue | 9 | Pages | 2470-81 |
| PubMed ID | 19714576 | Mgi Jnum | J:152143 |
| Mgi Id | MGI:4356351 | Doi | 10.1002/eji.200939325 |
| Citation | Rutitzky LI, et al. (2009) T-bet protects against exacerbation of schistosome egg-induced immunopathology by regulating Th17-mediated inflammation. Eur J Immunol 39(9):2470-81 |
| abstractText | C57BL/6 mice infected with Schistosoma mansoni naturally develop mild CD4(+) T-cell-mediated immunopathology characterized by small hepatic granulomas around parasite eggs. However, immunization with soluble egg Ag in CFA markedly exacerbates the lesions by inducing a potent proinflammatory environment with high levels of IFN-gamma and IL-17, which are signature cytokines of distinct Th1- versus Th17-cell lineages. To determine the relative role of these subsets in disease exacerbation, we examined mice deficient in T-bet (T-bet(-/-)), which is required for Th1 differentiation and IFN-gamma production. We now report that immunization with soluble egg Ag in CFA caused a significantly greater enhancement of egg-induced hepatic immunopathology in T-bet(-/-) mice compared with WT controls, and analysis of their granulomas disclosed a higher proportion of activated DC and CD4(+) T cells, as well as a marked influx of neutrophils. The absence of IFN-gamma in the T-bet(-/-) mice correlated with a marked increase in IL-23p19, IL-17 and TNF-alpha in granulomas and MLN. In contrast, T-bet(-/-) mice had lower levels of IL-4, IL-5 and IL-10 and a reduction in FIZZ1 and FoxP3 expression, suggesting diminished regulatory activity, respectively, by alternatively activated macrophages and Treg. These findings demonstrate that T-bet-dependent signaling negatively regulates Th17-mediated immunopathology in severe schistosomiasis. |
