Journal article
Subepidermal blistering induced by human autoantibodies to BP180 requires innate immune players in a humanized bullous pemphigoid mouse model
Journal of autoimmunity, Vol.31(4), pp.331-338
2008
DOI: 10.1016/j.jaut.2008.08.009
PMID: 18922680
Abstract
Bullous pemphigoid (BP) is a cutaneous autoimmune inflammatory disease associated with subepidermal blistering and autoantibodies against BP180, a transmembrane collagen and major component of the hemidesmosome. Numerous inflammatory cells infiltrate the upper dermis in BP. IgG autoantibodies in BP fix complement and target multiple BP180 epitopes that are highly clustered within a non-collagen linker domain, termed NC16A. Anti-BP180 antibodies induce BP in mice. In this study, we generated a humanized mouse strain, in which the murine BP180NC14A is replaced with the homologous human BP180NC16A epitope cluster region. We show that the humanized NC16A (NC16A+/+) mice injected with anti-BP180NC16A autoantibodies develop BP-like subepidermal blisters. The F(ab′)
2 fragments of pathogenic IgG fail to activate the complement cascade and are no longer pathogenic. The NC16A+/+ mice pretreated with mast cell activation blocker or depleted of complement or neutrophils become resistant to BP. These findings suggest that the humoral response in BP critically depends on innate immune system players.
Details
- Title: Subtitle
- Subepidermal blistering induced by human autoantibodies to BP180 requires innate immune players in a humanized bullous pemphigoid mouse model
- Creators
- Zhi Liu - Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAWen Sui - Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAMinglang Zhao - Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAZhuowei Li - Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USANing Li - Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USARandy Thresher - Department of Genetics and Animal Models core, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAGeorge J Giudice - Department of Dermatology, University of Iowa, Iowa City, USAJanet A Fairley - Department of Dermatology, University of Iowa, Iowa City, USACassian Sitaru - Department of Dermatology, University of Lübeck, GermanyDetlef Zillikens - Department of Dermatology, University of Lübeck, GermanyGang Ning - The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USAM. Peter Marinkovich - Department of Dermatology, Stanford University, Stanford, CA 94305, USALuis A Diaz - Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Resource Type
- Journal article
- Publication Details
- Journal of autoimmunity, Vol.31(4), pp.331-338
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.jaut.2008.08.009
- PMID
- 18922680
- ISSN
- 0896-8411
- eISSN
- 1095-9157
- Language
- English
- Date published
- 2008
- Academic Unit
- Dermatology
- Record Identifier
- 9984025437002771
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