Linked Life Data

20089696

Source:http://linkedlifedata.com/resource/pubmed/id/20089696

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-2-4
pubmed:abstractText
Bullous pemphigoid (BP), the most common autoimmune blistering disease, is caused by autoantibodies against type XVII collagen (COL17). To establish an active stable BP animal model that demonstrates the persistent inflammatory skin lesions initiated by the anti-human COL17 Abs, we used COL17-humanized (COL17(m-/-,h+)) mice that we recently produced. First, we generated immunodeficient Rag-2(-/-)/COL17-humanized mice by crossing Rag-2(-/-) mice with COL17-humanized mice. Then, splenocytes from wild-type mice that had been immunized by grafting of human COL17-transgenic mouse skin were transferred into Rag-2(-/-)/COL17-humanized mice. The recipient mice continuously produced anti-human COL17 IgG Abs in vivo and developed blisters and erosions corresponding to clinical, histological, and immunopathological features of BP, although eosinophil infiltration, one of the characteristic histological findings observed in BP patients, was not detected in the recipients. Although the depletion of CD8(+) T cells from the immunized splenocytes was found to produce no effects in the recipients, the depletion of CD4(+) T cells as well as CD45R(+) B cells was found to inhibit the production of anti-human COL17 IgG Abs in the recipients, resulting in no apparent clinical phenotype. Furthermore, we demonstrated that cyclosporin A significantly suppressed the production of anti-human COL17 IgG Abs and prevented the development of the BP phenotype in the treated recipients. Although this model in an immunodeficient mouse does not exactly reproduce the induction mechanism of BP in human patients, this unique experimental system targeting humanized pathogenic Ag allows us to investigate ongoing autoimmune responses to human molecules in experimental animal models.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
184
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2166-74
pubmed:meshHeading
pubmed-meshheading:20089696-Animals, pubmed-meshheading:20089696-Antigens, CD45, pubmed-meshheading:20089696-Autoantibodies, pubmed-meshheading:20089696-Autoantigens, pubmed-meshheading:20089696-B-Lymphocyte Subsets, pubmed-meshheading:20089696-CD4-Positive T-Lymphocytes, pubmed-meshheading:20089696-Disease Models, Animal, pubmed-meshheading:20089696-Female, pubmed-meshheading:20089696-Gene Targeting, pubmed-meshheading:20089696-Humans, pubmed-meshheading:20089696-Immunoglobulin G, pubmed-meshheading:20089696-Immunophenotyping, pubmed-meshheading:20089696-Lymphopenia, pubmed-meshheading:20089696-Mice, pubmed-meshheading:20089696-Mice, Inbred BALB C, pubmed-meshheading:20089696-Mice, Inbred C57BL, pubmed-meshheading:20089696-Mice, Knockout, pubmed-meshheading:20089696-Mice, Transgenic, pubmed-meshheading:20089696-Non-Fibrillar Collagens, pubmed-meshheading:20089696-Pemphigoid, Bullous
pubmed:year
2010
pubmed:articleTitle
A novel active mouse model for bullous pemphigoid targeting humanized pathogenic antigen.
pubmed:affiliation
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't