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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4581658
- author
- Schulze, Franziska S
; Beckmann, Tina
; Nimmerjahn, Falk
; Ishiko, Akira
; Collin, Mattias
LU
; Köhl, Jörg
; Goletz, Stephanie
; Zillikens, Detlef
; Ludwig, Ralf
and Schmidt, Enno
- organization
- publishing date
- 2014
- 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
- pmid:25043618
- 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
- 2016-04-01 10:30:27
- date last changed
- 2022-04-20 02:50:51
@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}},
doi = {{10.1016/j.ajpath.2014.05.007}},
volume = {{184}},
year = {{2014}},
}