| First Author | Schulze FS | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 8 | Pages | 2185-96 |
| PubMed ID | 25043618 | Mgi Jnum | J:213948 |
| Mgi Id | MGI:5586930 | Doi | 10.1016/j.ajpath.2014.05.007 |
| Citation | Schulze FS, et al. (2014) Fcgamma receptors III and IV mediate tissue destruction in a novel adult mouse model of bullous pemphigoid. Am J Pathol 184(8):2185-96 |
| abstractText | 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 Fcgamma receptors (FcgammaRs) I and III, the passive transfer model of epidermolysis bullosa acquisita completely depends on FcgammaRIV. To clarify this discrepancy, we developed a novel experimental model for BP using adult mice. Lesion formation was Fc mediated because gamma-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 FcgammaR-deficient mouse strains, tissue destruction was shown to be mediated by FcgammaRIV, FcgammaRIII, and FcgammaRIIB, whereas FcgammaRI 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 FcgammaRIV and depletion of granulocytes abolished skin blisters. Herein, we extended our knowledge about the importance of FcgammaRs 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. |
