Subepidermal blistering induced by human autoantibodies to BP180 requires innate immune players in a humanized bullous pemphigoid mouse model

Zhi Liu, Wen Sui, Minglang Zhao, Zhuowei Li, Ning Li, Randy Thresher, George J. Giudice, Janet A. Fairley, Cassian Sitaru, Detlef Zillikens, Gang Ning, M. Peter Marinkovich, Luis A. Diaz

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)331-338
Number of pages8
JournalJournal of Autoimmunity
Volume31
Issue number4
DOIs
StatePublished - Dec 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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