Doxycycline-Inducible Autoimmune Blistering Skin Disease Model

W. Nishie , M.D., Ph.D. • H. Shimizu , M.D., Ph.D. (*) Department of Dermatology , Hokkaido University Graduate School of Medicine , N15W7, Kita-ku , Sapporo 003-0835 , Japan e-mail: [email protected] Abstract Bullous pemphigoid (BP) is the most common autoimmune blistering disorder. BP autoantibodies target two hemidesmosomal components, collagen XVII (COL17) and BP230, with autoimmunity to COL17 being mainly involved in the development of the disease. BP most commonly affects the elderly, and systemic corticosteroids are widely used to treat blisters on the entire body. Therefore, severe cases are sometimes fatal. Toward developing innovative, disease-specifi c therapies with fewer adverse effects, faithful disease models are essential. However, it has been challenging to reproduce BP in animals, because of inter-species differences in the amino acid sequences of pathological epitopes on human and mouse COL17. Human IgG autoantibodies from BP patients are unable to bind with mouse COL17; thus, the passive transfer of BP-IgG into mice fails to induce blistering disease. To overcome inter-species differences, we have generated genetically modifi ed mice that express human but not mouse COL17 in skin. We call these “COL17-humanized mice”. Using these mice, we have produced different BP models to elucidate the BP pathomechanism and to produce novel BP therapies. Currently, another novel model is under development. Here, we introduce the BP models that we have developed by using a novel technique called “humanization of autoantigen”.