{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T08:34:45Z","timestamp":1789893285200,"version":"4.0.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2010,1,20]],"date-time":"2010-01-20T00:00:00Z","timestamp":1263945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 (COL17m\u2212\/\u2212,h+) mice that we recently produced. First, we generated immunodeficient Rag-2\u2212\/\u2212\/COL17\u2013humanized mice by crossing Rag-2\u2212\/\u2212 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\u2212\/\u2212\/COL17\u2013humanized 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.<\/jats:p>","DOI":"10.4049\/jimmunol.0903101","type":"journal-article","created":{"date-parts":[[2010,1,20]],"date-time":"2010-01-20T21:55:00Z","timestamp":1264024500000},"page":"2166-2174","source":"Crossref","is-referenced-by-count":72,"title":["A Novel Active Mouse Model for Bullous Pemphigoid Targeting Humanized Pathogenic Antigen"],"prefix":"10.1093","volume":"184","author":[{"given":"Hideyuki","family":"Ujiie","sequence":"first","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Shibaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Nishie","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Sawamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuki","family":"Tateishi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reine","family":"Moriuchi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjiang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , Sapporo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,1,20]]},"reference":[{"key":"2026012806301021300_r1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nm1496","article-title":"Humanization of autoantigen.","volume":"13","author":"Nishie","year":"2007","journal-title":"Nat. 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Dermatol."},{"key":"2026012806301021300_r5","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/1523-1747.ep12616615","article-title":"Cytoplasmic domain of the 180-kD bullous pemphigoid antigen, a hemidesmosomal component: molecular and cell biologic characterization.","volume":"99","author":"Hopkinson","year":"1992","journal-title":"J. Invest. Dermatol."},{"key":"2026012806301021300_r6","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1111\/1523-1747.ep12292701","article-title":"Bullous pemphigoid and cicatricial pemphigoid autoantibodies react with ultrastructurally separable epitopes on the BP180 ectodomain: evidence that BP180 spans the lamina lucida.","volume":"108","author":"B\u00e9dane","year":"1997","journal-title":"J. Invest. 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