Establishment of new mouse model for allergic dermatitis showing severe fibrosis.

Abstract

Allergic dermatitis (AD) is a skin disease characterized by a chronic inflammation caused by immune dysregulation. In the histopathology of patients with AD, there are several features, such as accumulation of eosinophils and mast cells, hyperkeratosis, and dermal fibrosis which are related to the exacerbation of AD. Mast cells and eosinophils are thought to be involved in fibrosis, but the details are unknown. Yama mouse is an inbred mouse showing genetically eosinophilia. If eosinophils have significant effect on fibrosis, it may be possible to establish a new AD model with severe fibrosis. In this study, AD was induced by applying dinitrofluorobenzene to mice auricle. Yama mice showed AD lesion with more severe dermal fibrosis with severe eosinophil infiltration than Balb/c and Nc/nga mice. The expression of transforming growth factor-β (TGF-β), a cytokine important for fibrosis, was not significantly different among Yama, Balb/c, and Nc/nga mice, while the expression of interleukin-4 (IL-4), which is also mediator of tissue fibrosis, was increased only in Yama mice. The results of this study showed that AD with more severe fibrosis could be induced in Yama mice than in Balb/c and Nc/nga mice. In Yama mice, it can be concluded that the severe fibrosis is TGF-β independent, and IL-4 would be the main mediator of severe fibrosis. This mouse model may be useful for elucidating the mechanism of fibrosis in chronic AD, and for conducting research leading to the development of new therapies.