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The role of additional extracellular targets of Col17 outside NC16A has not been unequivocally demonstrated. In this study, we showed that Col17 ectodomain\u2010reactive patient sera depleted in NC16A IgG induced dermal\u2013epidermal separation in a cryosection model indicating the pathogenic potential of anti\u2010Col17 non\u2010NC16A extracellular IgG. Moreover, injection of IgG targeting the murine Col17 NC14\u20131 domains (downstream of NC15A, the murine homologue of human NC16A) into C57BL\/6J mice resulted in erythematous skin lesions and erosions. Clinical findings were accompanied by IgG\/C3 deposits along the basement membrane and subepidermal blistering with inflammatory infiltrates. Disease development was significantly reduced in either Fc\u2010gamma receptor (Fc\u03b3R)\u2010 or complement\u20105a receptor\u20101 (C5aR1)\u2010deficient mice. Inhibition of the neonatal FcR (FcRn), an atypical Fc\u03b3R regulating IgG homeostasis, with the murine Fc fragment IgG2c\u2010ABDEG, a derivative of efgartigimod, reduced anti\u2010NC14\u20131 IgG levels, resulting in ameliorated skin inflammation compared with isotype\u2010treated controls. These data demonstrate that the pathogenic effects of IgG targeting the Col17 domain outside human NC16A\/murine NC15A are partly attributable to antibody\u2010mediated Fc\u03b3R\u2010 and C5aR1 effector mechanisms while pharmacological inhibition of the FcRn represents a promising treatment for BP. The mouse model of BP will be instrumental in further investigating the role of Col17 non\u2010NC16A\/NC15A extracellular epitopes and validating new therapies for this disease. \u00a9 2023 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6220","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T04:55:30Z","timestamp":1699246530000},"page":"161-174","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Bullous pemphigoid induced by\n                    <scp>IgG<\/scp>\n                    targeting type\n                    <scp>XVII<\/scp>\n                    collagen\n                    <scp>non\u2010NC16A<\/scp>\n                    \/\n                    <scp>NC15A<\/scp>\n                    extracellular domains is driven by Fc gamma receptor\u2010 and complement\u2010mediated effector mechanisms and is ameliorated by neonatal Fc receptor blockade"],"prefix":"10.1002","volume":"262","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3226-3935","authenticated-orcid":false,"given":"Manuela","family":"Pigors","sequence":"first","affiliation":[{"name":"L\u00fcbeck Institute of Experimental Dermatology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-3015","authenticated-orcid":false,"given":"Sabrina","family":"Patzelt","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Institute of Experimental Dermatology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Reichhelm","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Institute of Experimental 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