{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:21:24Z","timestamp":1790979684278,"version":"4.1.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"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":[[2013,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In autoimmune bullous dermatoses (AIBD), autoantibodies induce blisters on skin or mucous membranes, or both. Mechanisms of continued autoantibody production and blistering have been well characterized using AIBD animal models. Mechanisms leading to the initial autoantibody production, however, have not been investigated in detail. Epidermolysis bullosa acquisita (EBA) is an AIBD associated with autoantibodies to type VII collagen (COL7). The majority of EBA patients\u2019 sera recognize the noncollagenous domain 1, including the von Willebrand factor A\u2013like domain 2 (vWFA2). In experimental EBA induced by immunization with GST-COL7, disease manifestation depended on the genetic background, a Th1 polarization, and the GST-tag. In this model, nude mice neither produced autoantibodies nor blisters. It has remained uncertain which APC and T cell subsets are required for EBA induction. We established a novel EBA model by immunization with vWFA2 fused to intein (lacking the GST-tag). All tested mouse strains developed autoantibodies, but blisters were exclusively observed in mice carrying H2s. In immunized mice, CD4 T cells specific for vWFA2 were detected, and their induction required presence of B cells, dendritic cells, and macrophages. Anti-vWFA2 autoantibodies located at the lamina densa bound to the dermal side of salt-split skin and induced blisters when transferred into healthy mice. Absence of CD8 T cells at time of immunization had no effect, whereas depletion of CD4 T cells during the same time period delayed autoantibody production and blisters. Collectively, we demonstrate the pathogenic relevance of Abs targeting the vWFA2 domain of COL7 and show the requirement of APC-induced CD4 T cells to induce experimental EBA.<\/jats:p>","DOI":"10.4049\/jimmunol.1300310","type":"journal-article","created":{"date-parts":[[2013,8,19]],"date-time":"2013-08-19T21:29:04Z","timestamp":1376947744000},"page":"2978-2988","source":"Crossref","is-referenced-by-count":56,"title":["B Cells, Dendritic Cells, and Macrophages Are Required To Induce an Autoreactive CD4 Helper T Cell Response in Experimental Epidermolysis Bullosa Acquisita"],"prefix":"10.1093","volume":"191","author":[{"given":"Hiroaki","family":"Iwata","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Bieber","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Tiburzy","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navina","family":"Chrobok","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Kalies","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"The First Department of Dermatology, School of Medicine, Faculty of Medicine, Toho University , Ota-ku 143-8541,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Leineweber","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Ishiko","sequence":"additional","affiliation":[{"name":"The First Department of Dermatology, School of Medicine, Faculty of Medicine, Toho University , Ota-ku 143-8541,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Vorobyev","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Zillikens","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"K\u00f6hl","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]},{"name":"Division of Cellular and Molecular Immunology, Cincinnati Children\u2019s Hospital Medical Center and University of Cincinnati College of Medicine , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Westermann","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Seeger","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Manz","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf J","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,9,15]]},"reference":[{"key":"2025032405374868500_r1","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1084\/jem.188.10.1875","article-title":"CD4(+) T cells prevent spontaneous experimental autoimmune encephalomyelitis in anti-myelin basic protein T cell receptor transgenic mice","volume":"188","author":"Van de Keere","year":"1998","journal-title":"J. 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