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Recent evidence suggests that epidermal signals instruct the immune system in SLE, but whether epidermal IFN\u03ba alone is sufficient to drive lupus phenotypes has not been investigated. This study aimed to identify whether epidermal\u2010specific overexpression of IFN\u2010\u03ba (\n                      <jats:italic>Ifnk<\/jats:italic>\n                      ) results in lupus\u2010like cutaneous and systemic inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We compared 3\u2010month\u2010old (young) and 12\u2010month\u2010old (aged) Balb\/c mice who overexpress\n                      <jats:italic>Ifnk<\/jats:italic>\n                      in the epidermis under the keratin 14 promoter (transgenic [TG]) with age\u2010matched Balb\/c wild\u2010type mice and assessed local and systemic immune responses at baseline and after UV treatment. Skin lesions were assessed by histopathology, bulk RNA sequencing, and immunohistochemistry and subsequently compared to human cutaneous lupus erythematosus (CLE). Flow cytometry on lymph nodes and splenocytes at baseline and after UV treatment was performed to phenotype immune cell compositions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Ifnk<\/jats:italic>\n                      TG mice spontaneously developed CLE\u2010like lesions and systemic immune dysregulation. Lesions showed facial predominance, lymphocytic infiltration, immune complex deposition, and a transcriptional signature reflective of human CLE.\n                      <jats:italic>Ifnk<\/jats:italic>\n                      TG mice exhibited increased immune cell activation and spontaneous signs of systemic autoimmunity with higher anti\u2013double\u2010stranded DNA antibodies, lymphadenopathy, and splenomegaly but lacked signs of renal inflammation. UV treatment enhanced cutaneous inflammation and splenic T cell activation in\n                      <jats:italic>Ifnk<\/jats:italic>\n                      TG mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, we describe a new CLE mouse model that recapitulates features of human CLE and substantiates the role of epidermal IFN\u03ba as a driver of CLE, photosensitivity, and systemic inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.43350","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T07:54:22Z","timestamp":1754639662000},"page":"184-197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Epidermal Interferon\u2010\u03ba Drives Cutaneous Lupus\u2010Like Lesions, Photosensitivity, and Systemic Autoimmunity In Vivo"],"prefix":"10.1002","volume":"78","author":[{"given":"Benjamin","family":"Klein","sequence":"first","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Colesa","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Gao","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Lowe","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey E.","family":"McNeely","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Kim","family":"Nguyen","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Henning","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrnaz","family":"Gharaee\u2010Kermani","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B.","family":"Hodgin","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob W. 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