Voskas Daniel, Babichev Yael, Ling Ling S, Alami Jennifer, Shaked Yuval, Kerbel Robert S, Ciruna Brian, Dumont Daniel J
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
J Leukoc Biol. 2008 Jul;84(1):59-67. doi: 10.1189/jlb.0607347. Epub 2008 May 1.
Although mouse models of inflammatory skin diseases such as psoriasis and atopic dermatitis fail to completely phenocopy disease in humans, they provide invaluable tools to examine the molecular and cellular mechanisms responsible for the epidermal hyperplasia, inflammation, and excess angiogenesis observed in human disease. We have previously characterized a tyrosine kinase with immunoglobin-like and epidermal growth factor-like domain-2 (Tie-2) transgenic mouse model of an inflammatory skin disease exhibiting these features. More specifically, we demonstrated that the inflammatory component consisted of increased infiltration of CD3-positive T lymphocytes and mast cells in the skin. Here, we further characterize the inflammatory component in the blood and skin of Tie-2 transgenic mice at cellular and molecular levels. We observed increased numbers of CD3-positive T lymphocytes in the blood and increased infiltration of eosinophils in the skin. Furthermore, we characterized cytokine protein and gene expression in the blood and skin, respectively, and observed the deregulated expression of cytokines associated with Th1 and eosinophil immune responses. Interestingly, treatment of Tie-2 transgenic mice with anti-CD4 antibody appeared to resolve aspects of inflammation but did not resolve epidermal hyperplasia, suggesting an important role for eosinophils in mediating the inflammatory skin disease observed in Tie-2 transgenic mice.
尽管诸如银屑病和特应性皮炎等炎症性皮肤病的小鼠模型无法完全模拟人类疾病,但它们为研究导致人类疾病中观察到的表皮增生、炎症和过度血管生成的分子和细胞机制提供了宝贵的工具。我们之前已对一种具有免疫球蛋白样和表皮生长因子样结构域-2(Tie-2)的炎症性皮肤病转基因小鼠模型进行了表征,该模型展现出这些特征。更具体地说,我们证明炎症成分包括皮肤中CD3阳性T淋巴细胞和肥大细胞浸润增加。在此,我们在细胞和分子水平上进一步表征Tie-2转基因小鼠血液和皮肤中的炎症成分。我们观察到血液中CD3阳性T淋巴细胞数量增加,皮肤中嗜酸性粒细胞浸润增加。此外,我们分别对血液和皮肤中的细胞因子蛋白和基因表达进行了表征,并观察到与Th1和嗜酸性粒细胞免疫反应相关的细胞因子表达失调。有趣的是,用抗CD4抗体治疗Tie-2转基因小鼠似乎能缓解部分炎症,但不能缓解表皮增生,这表明嗜酸性粒细胞在介导Tie-2转基因小鼠中观察到的炎症性皮肤病中起重要作用。