{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T18:31:15Z","timestamp":1782757875490,"version":"3.54.5"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR070276"],"award-info":[{"award-number":["AR070276"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR072694"],"award-info":[{"award-number":["AR072694"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32OD011130"],"award-info":[{"award-number":["T32OD011130"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bullous pemphigoid (BP) is the most common autoimmune bullous skin disease of humans and is characterized by eosinophilic inflammation and circulating and tissue-bound IgG and IgE autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. The noncollagenous 16A domain (NC16A) of BP180 has been found to contain major epitopes recognized by autoantibodies in BP. We recently established the pathogenicity of anti-NC16A IgE through passive transfer of patient-derived autoantibodies to double-humanized mice that express the human high-affinity IgE receptor, Fc\u03b5RI, and human NC16A domain (Fc\u03b5RI\/NC16A). In this model, anti-NC16A IgEs recruit eosinophils to mediate tissue injury and clinical disease in Fc\u03b5RI\/NC16A mice. The objective of this study was to characterize the molecular and cellular events that underlie eosinophil recruitment and eosinophil-dependent tissue injury in anti-NC16A IgE-induced BP. We show that anti-NC16A IgEs significantly increase levels of key eosinophil chemoattractants, eotaxin-1 and eotaxin-2, as well as the proteolytic enzyme matrix metalloproteinase-9 (MMP-9) in the lesional skin of Fc\u03b5RI\/NC16A mice. Importantly, neutralization of eotaxin-1, but not eotaxin-2, and blockade of the main eotaxin receptor, CCR3, drastically reduce anti-NC16A IgE-induced disease activity. We further show that anti-NC16A IgE\/NC16A immune complexes induce the release of MMP-9 from eosinophils, and that MMP-9\u2013deficient mice are resistant to anti-NC16A IgE-induced BP. Lastly, we find significantly increased levels of eotaxin-1, eotaxin-2, and MMP-9 in blister fluids of BP patients. Taken together, this study establishes the eotaxin-1\/CCR3 axis and MMP-9 as key players in anti-NC16A IgE-induced BP and candidate therapeutic targets for future drug development and testing.<\/jats:p>","DOI":"10.4049\/jimmunol.2300080","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T14:42:52Z","timestamp":1694011372000},"page":"1216-1223","source":"Crossref","is-referenced-by-count":15,"title":["The Eotaxin-1\/CCR3 Axis and Matrix Metalloproteinase-9 Are Critical in Anti-NC16A IgE-Induced Bullous Pemphigoid"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6833-0167","authenticated-orcid":false,"given":"Tyler J M","family":"Jordan","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC"},{"name":"Department of Clinical Sciences, North Carolina State University , Raleigh, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC"},{"name":"Department of Dermatology, Wuhan No. 1 Hospital , Wuhan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0185-983X","authenticated-orcid":false,"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-8207","authenticated-orcid":false,"given":"Susan","family":"Burette","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Wuhan No. 1 Hospital , Wuhan ,","place":["China"]},{"name":"Dermatology Hospital of Southern Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-4652","authenticated-orcid":false,"given":"Liuqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Wuhan No. 1 Hospital , Wuhan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7692-6446","authenticated-orcid":false,"given":"Donna A","family":"Culton","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8731-6267","authenticated-orcid":false,"given":"Songmei","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9185-3548","authenticated-orcid":false,"given":"Paul","family":"Googe","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2230-1328","authenticated-orcid":false,"given":"Nancy E","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC"},{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7308-292X","authenticated-orcid":false,"given":"Luis A","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-9585","authenticated-orcid":false,"given":"Zhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC"},{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, NC"},{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill , Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"2025020406151393600_r1","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0140-6736(12)61140-4","article-title":"Pemphigoid diseases","volume":"381","author":"Schmidt","year":"2013","journal-title":"Lancet"},{"key":"2025020406151393600_r2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s12016-017-8633-4","article-title":"Autoimmune subepidermal bullous diseases of the skin and mucosae: clinical features, diagnosis, and management","volume":"54","author":"Amber","year":"2018","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"2025020406151393600_r3","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jaci.2020.02.013","article-title":"Autoimmune bullous skin diseases, pemphigus and pemphigoid","volume":"145","author":"Egami","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025020406151393600_r4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/1523-1747.ep12616580","article-title":"Cloning and primary structural analysis of the bullous pemphigoid autoantigen BP180","volume":"99","author":"Giudice","year":"1992","journal-title":"J. Invest. Dermatol."},{"key":"2025020406151393600_r5","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1111\/1523-1747.ep12337492","article-title":"Tight clustering of extracellular BP180 epitopes recognized by bullous pemphigoid autoantibodies","volume":"109","author":"Zillikens","year":"1997","journal-title":"J. Invest. 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