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Published online before print May 1, 2008

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(Journal of Leukocyte Biology. 2008;84:59-67.)
© 2008 by Society for Leukocyte Biology

An eosinophil immune response characterizes the inflammatory skin disease observed in Tie-2 transgenic mice

Daniel Voskas^*,,1,2, Yael Babichev^*,,1, Ling S. Ling^*,, Jennifer Alami, Yuval Shaked, Robert S. Kerbel^*,,, Brian Ciruna^,¶ and Daniel J. Dumont^*,,,3

Departments of
^* Medical Biophysics and
Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada;
Division of Molecular and Cellular Biology, Sunnybrook Research Institute, Toronto, Ontario, Canada;
Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada; and
^¶ Department of Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada

³Correspondence: Sunnybrook Research Institute, 2075 Bayview Avenue, Research Building, S-227, Toronto, Ontario, Canada, M4N 3M5. E-mail: dan.dumont{at}sri.ca

ABSTRACT

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.

Key Words: angiopoietin • eotaxin • antibody array • blood • inflammation