{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T08:34:53Z","timestamp":1789893293417,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_146215"],"award-info":[{"award-number":["310030_146215"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_166473"],"award-info":[{"award-number":["310030_166473"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2017,7]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Bullous pemphigoid (\n BP<\/jats:styled-content>\n ) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue\u2010bound and circulating autoantibodies to the hemidesmosomal antigens\n BP<\/jats:styled-content>\n 180 and\n BP<\/jats:styled-content>\n 230. Although eosinophils and their toxic mediators are found abundantly in\n BP<\/jats:styled-content>\n lesions, their role in blister formation has remained unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To investigate the role of eosinophils in the pathogenesis of\n BP<\/jats:styled-content>\n with a specific focus on blister formation and to define conditions inducing dermal\u2013epidermal separation (\n DES<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In an\n ex vivo<\/jats:italic>\n human model of\n BP<\/jats:styled-content>\n , normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of\n BP<\/jats:styled-content>\n autoantibodies, brefeldin A, diphenyleneiodonium,\n DN<\/jats:styled-content>\n ase or blocking F(ab\u2032)\n 2<\/jats:sub>\n fragments to\n CD<\/jats:styled-content>\n 16,\n CD<\/jats:styled-content>\n 18,\n CD<\/jats:styled-content>\n 32 and\n CD<\/jats:styled-content>\n 64. Dermal\u2013epidermal separation was assessed by light microscopy studies and quantified using\n Fiji<\/jats:sc>\n software.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Following activation with\n IL<\/jats:styled-content>\n \u20105 and in the presence of\n BP<\/jats:styled-content>\n autoantibodies, eosinophils induced separation along the dermal\u2013epidermal junction of\n ex vivo<\/jats:italic>\n skin. Dermal\u2013epidermal separation was significantly reduced by blocking any of the following: Fc\u03b3 receptor binding (\n P<\/jats:italic>\n = 0.048), eosinophil adhesion (\n P<\/jats:italic>\n = 0.046), reactive oxygen species (\n ROS<\/jats:styled-content>\n ) production (\n P<\/jats:italic>\n = 0.002), degranulation (\n P<\/jats:italic>\n < 0.0001) or eosinophil extracellular trap (\n EET<\/jats:styled-content>\n ) formation (\n P<\/jats:italic>\n = 0.048).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our results provide evidence that\n IL<\/jats:styled-content>\n \u20105\u2010activated eosinophils directly contribute to\n BP<\/jats:styled-content>\n blister formation in the presence of\n BP<\/jats:styled-content>\n autoantibodies. Dermal\u2013epidermal separation by\n IL<\/jats:styled-content>\n \u20105\u2010activated eosinophils depends on adhesion and Fc\u03b3 receptor activation, requires elevated\n ROS<\/jats:styled-content>\n production and degranulation and involves\n EET<\/jats:styled-content>\n formation. Thus, targeting eosinophils may be a promising therapeutic approach for\n BP<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/all.13131","type":"journal-article","created":{"date-parts":[[2017,1,30]],"date-time":"2017-01-30T17:46:48Z","timestamp":1485798408000},"page":"1105-1113","source":"Crossref","is-referenced-by-count":103,"title":["Evidence for a role of eosinophils in blister formation in bullous pemphigoid"],"prefix":"10.1111","volume":"72","author":[{"given":"E.","family":"de Graauw","sequence":"first","affiliation":[{"name":"Institute of Pharmacology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Sitaru","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Centre for Biological Signaling Studies (BIOSS) University Medical Center Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Horn","sequence":"additional","affiliation":[{"name":"Centre of Laboratory Medicine Inselspital Bern University Hospital Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Borradori","sequence":"additional","affiliation":[{"name":"Department of Dermatology Inselspital Bern University Hospital University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9855-4305","authenticated-orcid":false,"given":"S.","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.\u2010U.","family":"Simon","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8965-9407","authenticated-orcid":false,"given":"D.","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Dermatology Inselspital Bern University Hospital University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2015.05.005"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.02.010"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.10.050"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1855"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2012.02868.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.01.026"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2011.02694.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yadr.2007.07.013"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clindermatol.2011.03.005"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3335"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.04.012"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.1998.02169.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2000.03599.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117196"},{"key":"e_1_2_8_16_1","first-page":"897","article-title":"Deposition of eosinophil granule proteins precedes blister formation in bullous pemphigoid. Comparison with neutrophil and mast cell granule proteins","volume":"148","author":"Borrego L","year":"1996","journal-title":"Am J Pathol"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4362.1995.tb01562.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.11.002"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13717"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2002.01720.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2004.06245.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199910073411503"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.03.042"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2005.00322.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbbm.2005.10.003"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.5.3398"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.4049\/jimmunol.155.5.2631","article-title":"A crucial role for beta 2 integrin in the activation of eosinophils stimulated by IgG","volume":"155","author":"Kaneko M","year":"1995","journal-title":"J Immunol"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2157"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.10"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2011.01318.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119639"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.7.3987"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-007-0790-5"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12883"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.1999.02907.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1985.tb15628.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116856"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116368"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.151.10.5742"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1999.00497.x"},{"key":"e_1_2_8_42_1","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.4049\/jimmunol.145.9.2950","article-title":"Effects of IFN on human eosinophils in comparison with other cytokines. A novel class of eosinophil activators with delayed onset of action","volume":"145","author":"Valerius T","year":"1990","journal-title":"J Immunol"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.148.5.1471"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020531005776"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(00)90168-3"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.11.035"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12146.x"},{"key":"e_1_2_8_48_1","doi-asserted-by":"crossref","first-page":"6901","DOI":"10.4049\/jimmunol.162.11.6901","article-title":"Does IgE bind to and activate eosinophils from patients with allergy?","volume":"162","author":"Kita H","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_8_49_1","doi-asserted-by":"crossref","first-page":"6893","DOI":"10.4049\/jimmunol.162.11.6893","article-title":"Intracellular expression and release of Fc epsilon RI alpha by human eosinophils","volume":"162","author":"Seminario MC","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.1992.tb03185.x"},{"key":"e_1_2_8_51_1","first-page":"264","article-title":"Fc gamma and CD11\/CD18 receptor expression on normal density and low density human eosinophils","volume":"69","author":"Hartnell A","year":"1990","journal-title":"Immunology"},{"key":"e_1_2_8_52_1","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1001\/archderm.1989.01670200055008","article-title":"Evidence for eosinophil degranulation in the pathogenesis of herpes gestationis","volume":"125","author":"Scheman AJ","year":"1989","journal-title":"Arch Dermatol"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.1992.tb03224.x"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.111.1.81"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1997.0252"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010814-124407"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fall.13131","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.13131","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T23:05:07Z","timestamp":1696374307000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.13131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3]]},"references-count":55,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1111\/all.13131"],"URL":"https:\/\/doi.org\/10.1111\/all.13131","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3]]}}}