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Gene array data from GSE184989 (CLE, n = 68; control, n = 4), single\u2010cell RNA sequencing data from GSE186476 (CLE, n = 7; control, n = 14), and AMP Phase 1\u2010Metro (SLE, n = 17) were used. In vitro experiments further examined the expression of p21\n                      <jats:sup>WAF1\/CIP1<\/jats:sup>\n                      , Type I interferon (IFN), HLA class I (HLA\u2010I), and epidermal growth factor receptor (EGFR) signaling. Pharmacological clearance of senescent cells was performed using the senolytic drug fisetin in the SLE mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      p21\n                      <jats:sup>WAF1\/CIP1<\/jats:sup>\n                      \u2010high senescent epidermal basal cells in patients with CLE exhibit high Type I IFN expression. These cells enhance IFN signaling in surrounding normal epidermal basal cells, leading to increased HLA\u2010I expression. In contrast, senescent epidermal cells up\u2010regulate epidermal growth factor receptor signaling, which downregulates HLA\u2010I expression, allowing them to evade immune surveillance. This heterogeneity of HLA\u2010I expression promotes CD8\u2010positive T\u2010mediated toxicity against normal epidermal basal cells, resulting in their apoptosis. Pharmacological clearance of senescent epidermal basal cells improved SLE\u2010like skin lesions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Senescent cells create a microenvironment that directs cytotoxic T cell\u2010mediated responses against normal epidermis in patients with CLE, contributing to disease pathology. Targeting senescent cells and their signaling pathways may offer novel therapeutic strategies for patients with skin lesions from CLE and SLE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.43244","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T06:40:16Z","timestamp":1747636816000},"page":"1713-1725","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>Orchestration of Skin Pathology in Cutaneous Lupus Erythematosus by HLA<\/scp>\n                    Class I Down\u2010Regulated Senescent Epidermal Basal Cells"],"prefix":"10.1002","volume":"77","author":[{"given":"Sena","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Graduate School of Health Sciences, Hokkaido University  Sapporo 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