{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:48:24Z","timestamp":1787068104700,"version":"build-2736575974"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"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":[[2011,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The environment encountered in secondary lymphoid organs (e.g., lymph nodes) influences the outcome of immune responses. Immunization of mice with type VII collagen, an adhesion protein expressed at the cutaneous basement membrane, induces experimental epidermolysis bullosa acquisita (EBA). In this model, clinical disease is associated with the H2s haplotype of the MHC found in SJL\/J mice. Most other strains (e.g., BALB\/c, C57BL\/6, NZM2410\/J) are resistant to clinical disease, despite autoantibody production. Comparison of autoantibody response in EBA-resistant and -susceptible mice showed an IgG2-dominated response in the latter. We hypothesized that EBA susceptibility is due to specific cytokine gene expression in draining lymph nodes (dLN). To challenge this hypothesis, EBA-susceptible (SJL\/J) and -resistant (BALB\/c, C57BL\/6) mice were immunized with type VII collagen, followed by analysis of clinical phenotype, subclasses of circulating and tissue-bound autoantibodies, complement activation, and cytokine gene expression in dLN. Disease manifestation was associated with induction of complement-fixing autoantibodies, confirming previous observations. Furthermore, however, IFN-\u03b3\/IL-4 ratio in dLN of EBA-susceptible mice was significantly increased compared with EBA-resistant strains, suggesting a Th1 polarization. Immunization of H2s-congenic C57BL\/6 mice (B6.SJL-H2s) led to Th1 polarization in dLN and clinical disease. In addition to their cytokine milieu, EBA-susceptible and -resistant mice also differed regarding the expression of Fc\u03b3R on peripheral leukocytes, in which a higher Fc\u03b3RIV expression in SJL\/J and B6.SJL-H2s mice, compared with C57BL\/6, was associated with skin lesions. In summary, blistering in experimental EBA is regulated by both adaptive (divergent class switch recombination due to polarized cytokine expression) and innate (Fc\u03b3R expression) immune mechanisms.<\/jats:p>","DOI":"10.4049\/jimmunol.1100796","type":"journal-article","created":{"date-parts":[[2011,10,4]],"date-time":"2011-10-04T00:48:30Z","timestamp":1317689310000},"page":"5043-5050","source":"Crossref","is-referenced-by-count":49,"title":["Complement-Fixing Anti-Type VII Collagen Antibodies Are Induced in Th1-Polarized Lymph Nodes of Epidermolysis Bullosa Acquisita-Susceptible Mice"],"prefix":"10.1093","volume":"187","author":[{"given":"Christoph M","family":"Hammers","sequence":"first","affiliation":[{"name":"Excellence Cluster Inflammation at Interfaces , Schleswig-Holstein ,","place":["Germany"]},{"name":"Institute of Anatomy, Center for Structural and Cell Biology in Medicine, University of L\u00fcbeck , D-23538 L\u00fcbeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Bieber","sequence":"additional","affiliation":[{"name":"Excellence Cluster Inflammation at Interfaces , Schleswig-Holstein ,","place":["Germany"]},{"name":"Institute of Anatomy, Center for Structural and Cell Biology in Medicine, University of L\u00fcbeck , D-23538 L\u00fcbeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Kalies","sequence":"additional","affiliation":[{"name":"Excellence Cluster Inflammation at Interfaces , Schleswig-Holstein ,","place":["Germany"]},{"name":"Institute of Anatomy, Center for Structural and Cell Biology in Medicine, University of L\u00fcbeck , D-23538 L\u00fcbeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Banczyk","sequence":"additional","affiliation":[{"name":"Excellence Cluster Inflammation at Interfaces , Schleswig-Holstein ,","place":["Germany"]},{"name":"Institute of Anatomy, Center for Structural and Cell Biology in Medicine, University of L\u00fcbeck , D-23538 L\u00fcbeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph T","family":"Ellebrecht","sequence":"additional","affiliation":[{"name":"Excellence Cluster Inflammation at Interfaces , Schleswig-Holstein ,","place":["Germany"]},{"name":"Institute of Anatomy, Center for Structural and Cell Biology in Medicine, University of L\u00fcbeck , D-23538 L\u00fcbeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh M","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Excellence Cluster Inflammation at Interfaces , Schleswig-Holstein ,","place":["Germany"]},{"name":"Department of Dermatology, University of L\u00fcbeck , D-23538 L\u00fcbeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Zillikens","sequence":"additional","affiliation":[{"name":"Excellence Cluster Inflammation at Interfaces , Schleswig-Holstein ,","place":["Germany"]},{"name":"Department of Dermatology, University of L\u00fcbeck , D-23538 L\u00fcbeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf J","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Excellence Cluster Inflammation at Interfaces , Schleswig-Holstein ,","place":["Germany"]},{"name":"Department of Dermatology, University of L\u00fcbeck , D-23538 L\u00fcbeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Westermann","sequence":"additional","affiliation":[{"name":"Excellence Cluster Inflammation at Interfaces , Schleswig-Holstein ,","place":["Germany"]},{"name":"Institute of Anatomy, Center for Structural and Cell Biology in Medicine, University of L\u00fcbeck , D-23538 L\u00fcbeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,11,15]]},"reference":[{"key":"2025032410465646300_r1","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1056\/NEJM198404193101602","article-title":"Identification of the skin basement-membrane autoantigen in epidermolysis bullosa acquisita","volume":"310","author":"Woodley","year":"1984","journal-title":"N. Engl. J. Med."},{"key":"2025032410465646300_r2","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/1523-1747.ep12275978","article-title":"Epidermolysis bullosa acquisita antigen, a new major component of cutaneous basement membrane, is a glycoprotein with collagenous domains","volume":"86","author":"Woodley","year":"1986","journal-title":"J. Invest. Dermatol."},{"key":"2025032410465646300_r3","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1172\/JCI113373","article-title":"Epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen","volume":"81","author":"Woodley","year":"1988","journal-title":"J. Clin. Invest."},{"key":"2025032410465646300_r4","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1172\/JCI116774","article-title":"Epitope mapping of type VII collagen: identification of discrete peptide sequences recognized by sera from patients with acquired epidermolysis bullosa","volume":"92","author":"Lapiere","year":"1993","journal-title":"J. Clin. Invest."},{"key":"2025032410465646300_r5","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0002-9440(10)64182-X","article-title":"Autoantibodies to type VII collagen mediate Fcgamma-dependent neutrophil activation and induce dermal-epidermal separation in cryosections of human skin","volume":"161","author":"Sitaru","year":"2002","journal-title":"Am. J. Pathol."},{"key":"2025032410465646300_r6","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.jaut.2009.11.003","article-title":"Pathogenicity of IgG subclass autoantibodies to type VII collagen: induction of dermal-epidermal separation","volume":"34","author":"Recke","year":"2010","journal-title":"J. Autoimmun."},{"key":"2025032410465646300_r7","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.2353\/ajpath.2007.061212","article-title":"The cartilage matrix protein subdomain of type VII collagen is pathogenic for epidermolysis bullosa acquisita","volume":"170","author":"Chen","year":"2007","journal-title":"Am. J. Pathol."},{"key":"2025032410465646300_r8","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1172\/JCI200521386","article-title":"Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen","volume":"115","author":"Sitaru","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2025032410465646300_r9","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1111\/j.0022-202X.2005.23702.x","article-title":"Evidence that anti-type VII collagen antibodies are pathogenic and responsible for the clinical, histological, and immunological features of epidermolysis bullosa acquisita","volume":"124","author":"Woodley","year":"2005","journal-title":"J. Invest. Dermatol."},{"key":"2025032410465646300_r10","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/sj.jid.5700254","article-title":"Induction of epidermolysis bullosa acquisita in mice by passive transfer of autoantibodies from patients","volume":"126","author":"Woodley","year":"2006","journal-title":"J. Invest. Dermatol."},{"key":"2025032410465646300_r11","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.4049\/jimmunol.177.5.3461","article-title":"Induction of complement-fixing autoantibodies against type VII collagen results in subepidermal blistering in mice","volume":"177","author":"Sitaru","year":"2006","journal-title":"J. Immunol."},{"key":"2025032410465646300_r12","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/jid.2010.248","article-title":"Generation of antibodies of distinct subclasses and specificity is linked to H2s in an active mouse model of epidermolysis bullosa acquisita","volume":"131","author":"Ludwig","year":"2011","journal-title":"J. Invest. Dermatol."},{"key":"2025032410465646300_r13","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.det.2011.03.003","article-title":"Pathogenesis of epidermolysis bullosa acquisita","volume":"29","author":"Ludwig","year":"2011","journal-title":"Dermatol. Clin."},{"key":"2025032410465646300_r14","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.4049\/jimmunol.0901412","article-title":"T cells are required for the production of blister-inducing autoantibodies in experimental epidermolysis bullosa acquisita","volume":"184","author":"Sitaru","year":"2010","journal-title":"J. Immunol."},{"key":"2025032410465646300_r15","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/383787a0","article-title":"Functional diversity of helper T lymphocytes","volume":"383","author":"Abbas","year":"1996","journal-title":"Nature"},{"key":"2025032410465646300_r16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0167-5699(97)01237-1","article-title":"How the MHC selects Th1\/Th2 immunity","volume":"19","author":"Murray","year":"1998","journal-title":"Immunol. Today"},{"key":"2025032410465646300_r17","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0167-5699(97)80019-9","article-title":"The Th1\/Th2 paradigm","volume":"18","author":"Romagnani","year":"1997","journal-title":"Immunol. Today"},{"key":"2025032410465646300_r18","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1111\/j.1365-2133.2010.09680.x","article-title":"Clearance rates of circulating and tissue-bound autoantibodies to type VII collagen in experimental epidermolysis bullosa acquisita","volume":"162","author":"Kasperkiewicz","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"2025032410465646300_r19","doi-asserted-by":"crossref","first-page":"6135","DOI":"10.1182\/blood-2010-10-314609","article-title":"Heat-shock protein 90 inhibition in autoimmunity to type VII collagen: evidence that nonmalignant plasma cells are not therapeutic targets","volume":"117","author":"Kasperkiewicz","year":"2011","journal-title":"Blood"},{"key":"2025032410465646300_r20","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/1523-1747.ep12506462","article-title":"Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker","volume":"78","author":"Bradley","year":"1982","journal-title":"J. Invest. Dermatol."},{"key":"2025032410465646300_r21","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/j.0022-202X.2005.23912.x","article-title":"Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation","volume":"125","author":"Ludwig","year":"2005","journal-title":"J. Invest. Dermatol."},{"key":"2025032410465646300_r22","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.4049\/jimmunol.174.5.2517","article-title":"Naive, effector, and memory T lymphocytes efficiently scan dendritic cells in vivo: contact frequency in T cell zones of secondary lymphoid organs does not depend on LFA-1 expression and facilitates survival of effector T cells","volume":"174","author":"Westermann","year":"2005","journal-title":"J. Immunol."},{"key":"2025032410465646300_r23","doi-asserted-by":"crossref","first-page":"741","DOI":"10.4049\/jimmunol.176.2.741","article-title":"T cell zones of lymphoid organs constitutively express Th1 cytokine mRNA: specific changes during the early phase of an immune response","volume":"176","author":"Kalies","year":"2006","journal-title":"J. Immunol."},{"key":"2025032410465646300_r24","doi-asserted-by":"crossref","first-page":"5457","DOI":"10.4049\/jimmunol.180.8.5457","article-title":"Nonoverlapping expression of IL10, IL12p40, and IFNgamma mRNA in the marginal zone and T cell zone of the spleen after antigenic stimulation","volume":"180","author":"Kalies","year":"2008","journal-title":"J. Immunol."},{"key":"2025032410465646300_r25","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri2206","article-title":"Fcgamma receptors as regulators of immune responses","volume":"8","author":"Nimmerjahn","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025032410465646300_r26","doi-asserted-by":"crossref","first-page":"6514","DOI":"10.4049\/jimmunol.178.10.6514","article-title":"The alternative pathway of complement activation is critical for blister induction in experimental epidermolysis bullosa acquisita","volume":"178","author":"Mihai","year":"2007","journal-title":"J. Immunol."},{"key":"2025032410465646300_r27","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1159\/000199434","article-title":"Interferon-gamma treatment accelerates and aggravates autoimmune pancreatitis in the MRL\/Mp-mouse","volume":"9","author":"Fitzner","year":"2009","journal-title":"Pancreatology"},{"key":"2025032410465646300_r28","first-page":"869","article-title":"Alteration of T helper cell subsets in the optic nerve of experimental autoimmune encephalomyelitis","volume":"25","author":"Tian","year":"2010","journal-title":"Int. J. Mol. Med."},{"key":"2025032410465646300_r29","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1164\/rccm.200805-666OC","article-title":"Resolution of allergic inflammation and airway hyperreactivity is dependent upon disruption of the T1\/ST2-IL-33 pathway","volume":"179","author":"Kearley","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025032410465646300_r30","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.4049\/jimmunol.174.5.2934","article-title":"Nonhealing infection despite Th1 polarization produced by a strain of Leishmania major in C57BL\/6 mice","volume":"174","author":"Anderson","year":"2005","journal-title":"J. Immunol."},{"key":"2025032410465646300_r31","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.yexmp.2010.03.002","article-title":"Inflammatory response and dynamics of lung T cell subsets in Th1, Th2 biased and Th2 deficient mice during the development of hypersensitivity pneumonitis","volume":"88","author":"Jimenez-Alvarez","year":"2010","journal-title":"Exp. Mol. Pathol."},{"key":"2025032410465646300_r32","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0196-9781(95)02104-3","article-title":"Aspergillus fumigatus peptides differentially express Th1 and Th2 cytokines","volume":"17","author":"Kurup","year":"1996","journal-title":"Peptides"},{"key":"2025032410465646300_r33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/j.1365-3083.2009.02363.x","article-title":"New production of eosinophils and the corresponding TH1\/TH2 balance in the lungs after allergen exposure in BALB\/c and C57BL\/6 mice","volume":"71","author":"Lu","year":"2010","journal-title":"Scand. J. Immunol."},{"key":"2025032410465646300_r34","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1189\/jlb.0407247","article-title":"Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice","volume":"83","author":"Daley","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"2025032410465646300_r35","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/path.1674","article-title":"Granulocyte-derived elastase and gelatinase B are required for dermal-epidermal separation induced by autoantibodies from patients with epidermolysis bullosa acquisita and bullous pemphigoid","volume":"204","author":"Shimanovich","year":"2004","journal-title":"J. Pathol."},{"key":"2025032410465646300_r36","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/eji.1830220239","article-title":"Major histocompatibility complex (MHC) control of CD4 T cell subset activation. II. A single peptide induces either humoral or cell-mediated responses in mice of distinct MHC genotype","volume":"22","author":"Murray","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"2025032410465646300_r37","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1600-065X.1991.tb00606.x","article-title":"Selective activation of Th1- and Th2-like cells in vivo: response to human collagen IV","volume":"123","author":"Pfeiffer","year":"1991","journal-title":"Immunol. Rev."},{"key":"2025032410465646300_r38","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/eji.1830270224","article-title":"The intensity of T cell receptor engagement determines the cytokine pattern of human allergen-specific T helper cells","volume":"27","author":"Carballido","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"2025032410465646300_r39","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0165-2478(00)00188-7","article-title":"Antigen dose defines T helper 1 and T helper 2 responses in the lungs of C57BL\/6 and BALB\/c mice independently of splenic responses","volume":"72","author":"Morokata","year":"2000","journal-title":"Immunol. Lett."},{"key":"2025032410465646300_r40","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.4049\/jimmunol.157.9.3893","article-title":"MHC genotype controls the capacity of ligand density to switch T helper (Th)-1\/Th-2 priming in vivo","volume":"157","author":"Schountz","year":"1996","journal-title":"J. Immunol."},{"key":"2025032410465646300_r41","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1172\/JCI200421055","article-title":"A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice","volume":"114","author":"Marietta","year":"2004","journal-title":"J. Clin. Invest."},{"key":"2025032410465646300_r42","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.4049\/jimmunol.1100596","article-title":"Repetitive immunization breaks tolerance to type XVII collagen and leads to bullous pemphigoid in mice","volume":"187","author":"Hirose","year":"2011","journal-title":"J. Immunol."},{"key":"2025032410465646300_r43","article-title":"FcgammaRIV promotes, while FcgammaRIIb protects from autoantibody-induced tissue damage in autoimmunity to type VII collagen","volume":"130","author":"Kasperkiewicz","year":"2010","journal-title":"J. Invest. Dermatol."},{"key":"2025032410465646300_r44","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/path.2157","article-title":"NADPH oxidase is required for neutrophil-dependent autoantibody-induced tissue damage","volume":"212","author":"Chiriac","year":"2007","journal-title":"J. Pathol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/187\/10\/5043\/61605967\/1100796.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/187\/10\/5043\/61605967\/1100796.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T02:10:33Z","timestamp":1743127833000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/187\/10\/5043\/7977275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2011,11,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1100796","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13407984.14778088","asserted-by":"object"}]},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,11]]},"published":{"date-parts":[[2011,11]]}}}