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Fcγ Receptors III and IV Mediate Tissue Destruction in a Novel Adult Mouse Model of Bullous Pemphigoid.

Schulze, Franziska S; Beckmann, Tina; Nimmerjahn, Falk; Ishiko, Akira; Collin, Mattias LU ; Köhl, Jörg; Goletz, Stephanie; Zillikens, Detlef; Ludwig, Ralf and Schmidt, Enno (2014) In American Journal of Pathology 184(8). p.2185-2196
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
184
issue
8
pages
2185 - 2196
publisher
American Society for Investigative Pathology
external identifiers
  • pmid:25043618
  • wos:000339533100006
  • scopus:84904705405
ISSN
1525-2191
DOI
10.1016/j.ajpath.2014.05.007
language
English
LU publication?
yes
id
afa8e27a-d9b6-4e1e-9831-1a7ef5a297ec (old id 4581658)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25043618?dopt=Abstract
date added to LUP
2014-08-08 21:15:35
date last changed
2017-10-29 03:12:11
@article{afa8e27a-d9b6-4e1e-9831-1a7ef5a297ec,
  abstract     = {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.},
  author       = {Schulze, Franziska S and Beckmann, Tina and Nimmerjahn, Falk and Ishiko, Akira and Collin, Mattias and Köhl, Jörg and Goletz, Stephanie and Zillikens, Detlef and Ludwig, Ralf and Schmidt, Enno},
  issn         = {1525-2191},
  language     = {eng},
  number       = {8},
  pages        = {2185--2196},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Fcγ Receptors III and IV Mediate Tissue Destruction in a Novel Adult Mouse Model of Bullous Pemphigoid.},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2014.05.007},
  volume       = {184},
  year         = {2014},
}