A novel active mouse model for bullous pemphigoid targeting humanized pathogenic antigen

Area of Science:

• Immunology
• Dermatology
• Animal Modeling

Background:

• Bullous pemphigoid (BP) is the most common autoimmune blistering disease.
• BP pathogenesis involves autoantibodies targeting type XVII collagen (COL17).
• Existing animal models do not fully replicate persistent inflammatory skin lesions.

Purpose of the Study:

• To establish an active, stable animal model for bullous pemphigoid (BP).
• To investigate autoimmune responses against human collagen XVII (COL17) in vivo.
• To characterize the cellular requirements for anti-COL17 autoantibody production.

Main Methods:

• Generation of immunodeficient Rag-2(-/-)/COL17-humanized mice.
• Transfer of splenocytes from wild-type mice immunized with human COL17-transgenic skin.
• Analysis of autoantibody production, clinical phenotype, and cellular depletions (CD4+, CD8+, CD45R+).
• Assessment of cyclosporin A effects on autoantibody production and disease phenotype.

Main Results:

• Recipient mice produced anti-human COL17 IgG autoantibodies and developed BP-like blisters and erosions.
• Depletion of CD4+ T cells and CD45R+ B cells inhibited autoantibody production and prevented disease.
• Cyclosporin A treatment suppressed autoantibody production and ameliorated the BP phenotype.
• Eosinophil infiltration, characteristic of human BP, was not observed in this model.

Conclusions:

• A novel immunodeficient mouse model using humanized COL17 mice can replicate key features of bullous pemphigoid.
• This model demonstrates the critical role of CD4+ T cells and B cells in anti-COL17 autoantibody production.
• The model provides a valuable platform for studying autoimmune responses to human COL17 and evaluating potential therapies.