Characterization of an animal model of atopic dermatitis

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DESCRIPTION (Taken from the application): Atopic dermatitis is a chronic, inflammatory skin disease that affects about 20% children between ages 3 and 11. The prevalence of atopic, dermatitis is increasing, particularly in the industrialized nations. Atopic dermatitis is characterized by pruritic skin rash clinically, T lymphocyte and mast cell infiltration histopathologically, and elevation of total serum IgE serologically. Although usually non-fatal, atopic dermatitis can cause significant morbidity. Clinical and laboratory data from studying of human patients suggests that atopic dermatitis may be caused by an imbalance of excessive activation of Th2-type lymphocytes over Thl-type lymphocytes, resulting in a Th2-biased immune response. However, the step-by-step immunological sequence of events accounting for the initiation, progression, and maintenance of the disease remain unclear. Furthermore, currently there is no available experimental animal model of atopic derrnatitis for dissecting these step-by-step events. The PI, Lawrence S. Chan, M.D., was trained as a fellow in Immuno-dermatology under Dr. Kevin D. Cooper, a cellular immunologist at the Univ. of Michigan. For the current proposal, the PI aims at characterizing a transgenic (Tg) mouse model that the PI has recently created. This experimental mouse model was generated by transgenically introduced critical Th2 cytokine IL-4 to the basal epidermis of Tg mice and the affected Tg mice has identical clinical, histopathological, microbiological, and serological characteristics as human atopic dermatitis. With the availability of this newly created mouse disease model, the PI can now move forward to further characterize this experimental model of atopic dermatitis with the following specific aims: 1). Determining the correlation of epidermal IL-4 in vivo protein expression and total serum IgE levels with clinical phenotype. 2). Determining the inflammatory cell types of skin lesions. 3). Characterizing the cytokine profiles of skin lesions. By parallel studying the natural history of atopic dermatitis and the immunological parameters, including lesional inflammatory cell and T cell subsets, lesional T cell cytokines, adhesion molecules, and total serum IgE, the PI aims at delineating the step-by-step immune events accounting for the initiation, progression, and maintenance of the disease. The likelihood of achieving these aims is supported by the PI's past experience in these areas of investigation and the assistance of Dr. Stephen D. Miller, an experienced cellular immunologist and the coinvestigator of the project. Delineating the characteristics of atopic dermatitis in this mouse disease model may shed light to the pathogenesis of atopic dermatitis in human patients, thereby lead to eventual target-specific immunological treatments for human patients suffering from atopic dermatitis.