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Mayumi Ueta, Junji Hamuro, Eiichiro Ueda, Norito Katoh, Masahiro Yamamoto, Kiyoshi Takeda, Shizuo Akira, Shigeru Kinoshita; Stat6-Independent Tissue Inflammation Occurs Selectively on the Ocular Surface and Perioral Skin of IκBζ−/− Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(8):3387-3394. doi: 10.1167/iovs.08-1691.
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purpose. IκBζ−/− mice have been reported to be affected by allergic dermatitis. This study was conducted to analyze the pathophysiological role of IκBζ and to address the functional relevance of Th2-mediated immune responses in the development of ocular surface inflammation and dermatitis by IκBζ−/− mice.
methods. BALB/c background IκBζ−/− mice were established without individual differences; IκBζ/Stat6 double-knockout (WKO) mice unable to produce Th2 cytokine were created; and microscopic-, histologic-, and immunochemical studies were performed. In IκBζ−/− mice the serum IgE levels were examined by ELISA, and quantitative PCR was used to study the gene expression of IFN-γ, IL4, IL10, TNFα, IL6, IL17α, and CCL11 in eyelid tissue.
results. IκBζ−/− mice exhibited a severe inflammatory phenotype on the ocular surface and perioral skin. The inflammatory infiltrates in the perioral skin consisted primarily of CD4+ and CD8+ cells; CD4+ and CD45R/B220+ cells were mainly detected in the conjunctiva. In eyelid and perioral skin tissue, the expression of IL-17α and of Th1 and Th2 cytokines, but not of CCL11, was augmented. IκBζ−/− and IκBζ+/− mice did not differ significantly in their serum total IgE levels before, 0 to 4 weeks, and 5 to 9 weeks after disease onset. IκBζ/Stat6 WKO mice showed the same or slightly more severe inflammation than did IκBζ−/− mice.
conclusions. IgE and Stat6 are not responsible for the immune pathologic response leading to the development of ocular surface and perioral skin inflammation in IκBζ−/− mice. IκBζ−/− mice may be a suitable model for Stevens-Johnson syndrome, but not for atopic dermatitis.
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