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Repetitive Immunization Breaks Tolerance to Type XVII Collagen and Leads to Bullous Pemphigoid in Mice
Repetitive Immunization Breaks Tolerance to Type XVII Collagen and Leads to Bullous Pemphigoid in Mice
- Source :
- The Journal of Immunology. 187:1176-1183
- Publication Year :
- 2011
- Publisher :
- The American Association of Immunologists, 2011.
-
Abstract
- Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease of the elderly associated with considerable morbidity and mortality. As unspecific immunosuppressants are still the mainstay of BP therapy, several animal models, based on the passive transfer of autoantibodies or immune cells, have been developed to obtain a better understanding of the pathogenesis of BP and evaluate novel therapeutic interventions. We describe in this study an experimental model inducing BP by immunization of immunocompetent mice with a recombinant form of the immunodominant 15th noncollagenous domain of murine BP180 (type XVII collagen). The homologous noncollagenous 16A domain of human BP180 has previously been identified as an immunodominant region in human BP. Immunization of female SJL/J mice with the murine peptide led to clinical disease within 14 wk in 56% of mice. In contrast, none of the other strains developed blisters despite the presence of autoantibodies. The clinical disease manifested for at least 8 wk without further manipulation. This novel immunization-induced model reflects key immunopathological characteristics of human BP, including binding of complement-fixing autoantibodies along the dermal–epidermal junction, elevated total IgE serum levels, and infiltration of skin lesions with eosinophilic granulocytes. The use of immunocompetent mice and the induction of sustained clinical disease not requiring additional interventions make this immunization-induced mouse model most suitable to further explore the pathogenesis of BP and novel therapeutic interventions for this and other autoantibody-mediated diseases.
- Subjects :
- Pathology
medicine.medical_specialty
Pemphigoid
Neutrophils
Immunology
Immunization, Secondary
Autoantigens
Pathogenesis
Mice
Immune system
Pemphigoid, Bullous
Eosinophilic
Immune Tolerance
medicine
Homologous chromosome
Animals
Immunology and Allergy
Complement Activation
Mice, Inbred BALB C
Vaccines, Synthetic
biology
business.industry
Autoantibody
Non-Fibrillar Collagens
medicine.disease
Eosinophils
Mice, Inbred C57BL
Vaccines, Virosome
Chemotaxis, Leukocyte
Disease Models, Animal
Mice, Inbred DBA
Immunoglobulin G
Vaccines, Subunit
biology.protein
Female
Binding Sites, Antibody
Bullous pemphigoid
Epidermis
Antibody
business
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 187
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....b727ebd7a72ddad08fa1659ba55f9e34
- Full Text :
- https://doi.org/10.4049/jimmunol.1100596