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As histologic inflammation is variable and non\u2010complement\u2010fixing IgG antibodies against laminin\u2010332 are the predominant class of autoantibodies deposited at the epidermal basement membrane zone, we hypothesized that complement\u2010independent pro\u2010inflammatory and blistering pathways existed similarly to that previously shown in bullous pemphigoid. As autoantibodies to laminin \u03b13 are most prevalent, we studied the major cellular response to blockade of laminin \u03b13 using a well\u2010characterized monoclonal antibody (P3H9\u20102). RNA\u2010seq revealed upregulation of numerous desmosomal genes (<jats:italic>DSG1<\/jats:italic>, <jats:italic>DSG3<\/jats:italic>, <jats:italic>DSC1<\/jats:italic>, <jats:italic>DSC3 and DSP<\/jats:italic>) as well as <jats:italic>KRT1<\/jats:italic> and <jats:italic>KRT10<\/jats:italic>. Additionally, P3H9\u20102\u2010treated cells demonstrated downregulation of most hemidesmosomal genes. A pro\u2010inflammatory response was not appreciated. Using pharmacological inhibitors, we identified both protein kinase C and NOTCH as key regulators of P3H9\u20102 induced differentiation. We lastly utilized 3D human skin equivalents to determine whether blockade of laminin \u03b13 would lead to delayed blistering, consistent with keratinocyte differentiation. Significant blistering was noted after 72\u00a0h of treatment, with only minimal separation at 24\u00a0h. In summary, blockade of laminin \u03b13 alters keratinocyte differentiation, representing a potential complement\u2010independent mechanism of blistering.<\/jats:p>","DOI":"10.1111\/exd.14501","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T07:39:22Z","timestamp":1637307562000},"page":"615-621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Gene expression profiling of laminin \u03b13\u2010blocked keratinocytes reveals an immune\u2010independent mechanism of blistering"],"prefix":"10.1111","volume":"31","author":[{"given":"Lei","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany E.","family":"Perez White","sequence":"additional","affiliation":[{"name":"Skin Tissue Engineering and Morphology (STEM) Core Feinberg 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