Fcγ receptors III and IV mediate tissue destruction in a novel adult mouse model of bullous pemphigoid

Franziska S. Schulze, Tina Beckmann, Falk Nimmerjahn, Akira Ishiko, Mattias Collin, Jörg Köhl, Stephanie Goletz, Detlef Zillikens, Ralf Ludwig, Enno Schmidt*

*Corresponding author for this work
30 Citations (Scopus)


Bullous pemphigoid (BP) and epidermolysis bullosa acquisita are subepidermal autoimmune blistering diseases mediated by autoantibodies against type XVII collagen (Col17) and Col7, respectively. For blister formation, Fc-mediated events, such as infiltration of inflammatory cells in the skin, complement activation, and release of proteases at the dermal-epidermal junction, are essential. Although in the neonatal passive transfer mouse model of BP, tissue destruction is mediated by Fcγ receptors (FcγRs) I and III, the passive transfer model of epidermolysis bullosa acquisita completely depends on FcγRIV. To clarify this discrepancy, we developed a novel experimental model for BP using adult mice. Lesion formation was Fc mediated because γ-chain-deficient mice and mice treated with anti-Col17 IgG, depleted from its sugar moiety at the Fc portion, were resistant to disease induction. By the use of various FcγR-deficient mouse strains, tissue destruction was shown to be mediated by FcγRIV, FcγRIII, and FcγRIIB, whereas FcγRI was not essential. Furthermore, anti-inflammatory mediators in already clinically diseased mice can be explored in the novel BP model, because the pharmacological inhibition of FcγRIV and depletion of granulocytes abolished skin blisters. Herein, we extended our knowledge about the importance of FcγRs in experimental BP and established a novel BP mouse model suitable to study disease development over a longer time period and explore novel treatment strategies in a quasi-therapeutic setting.

Original languageEnglish
JournalAmerican Journal of Pathology
Issue number8
Pages (from-to)2185-2196
Number of pages12
Publication statusPublished - 01.01.2014


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