{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:22Z","timestamp":1787030842421,"version":"build-2736575974"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"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":[[2014,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Complement activation and subsequent recruitment of inflammatory cells at the dermal\/epidermal junction are thought to be essential for blister formation in bullous pemphigoid (BP), an autoimmune blistering disease induced by autoantibodies against type XVII collagen (COL17); however, this theory does not fully explain the pathological features of BP. Recently, the involvement of complement-independent pathways has been proposed. To directly address the question of the necessity of the complement activation in blister formation, we generated C3-deficient COL17-humanized mice. First, we show that passive transfer of autoantibodies from BP patients induced blister formation in neonatal C3-deficient COL17-humanized mice without complement activation. By using newly generated human and murine mAbs against the pathogenic noncollagenous 16A domain of COL17 with high (human IgG1, murine IgG2), low (murine IgG1), or no (human IgG4) complement activation abilities, we demonstrate that the deposition of Abs, and not complements, is relevant to the induction of blister formation in neonatal and adult mice. Notably, passive transfer of BP autoantibodies reduced the amount of COL17 in lesional mice skin, as observed in cultured normal human keratinocytes treated with the same Abs. Moreover, the COL17 depletion was associated with a ubiquitin\/proteasome pathway. In conclusion, the COL17 depletion induced by BP autoantibodies, and not complement activation, is essential for the blister formation under our experimental system.<\/jats:p>","DOI":"10.4049\/jimmunol.1400095","type":"journal-article","created":{"date-parts":[[2014,9,26]],"date-time":"2014-09-26T23:29:33Z","timestamp":1411774173000},"page":"4415-4428","source":"Crossref","is-referenced-by-count":94,"title":["Bullous Pemphigoid Autoantibodies Directly Induce Blister Formation without Complement Activation"],"prefix":"10.1093","volume":"193","author":[{"given":"Hideyuki","family":"Ujiie","sequence":"first","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , 060-8638 Sapporo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsumasa","family":"Sasaoka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , 060-8638 Sapporo ,","place":["Japan"]},{"name":"Research Laboratory 3G, Research and Development Division, Nihon Pharmaceutical Co., Ltd. , 598-0061 Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , 060-8638 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 , 060-8638 Sapporo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Shinkuma","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , 060-8638 Sapporo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Natsuga","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hokkaido University Graduate School of Medicine , 060-8638 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 , 060-8638 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 , 060-8638 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 , 060-8638 Sapporo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,11,1]]},"reference":[{"key":"2025030707420671100_r1","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. 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