Orchestration of Skin Pathology in Cutaneous Lupus Erythematosus by HLA Class I Down-Regulated Senescent Epidermal Basal Cells.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40386939", "kind": "science-record", "revision": 3, "content_hash": "sha256:1f2e58afef2c3adf91afd0ab07822bdacd3a5935e280385c06943531304136e7", "created_at": "2026-11-01T20:30:32Z", "updated_at": "2026-11-01T22:14:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Orchestration of Skin Pathology in Cutaneous Lupus Erythematosus by HLA Class I Down-Regulated Senescent Epidermal Basal Cells.", "doi": "10.1002/art.43244", "pmid": "40386939", "authors": ["Sena Yamamoto", "Yuki Saito", "Tsukasa Sato", "Seina Nakano", "Dain Kasseki", "Ayaka Nagao", "Norihiro Miura", "Kentaro Nagaoka", "Arisa Kita", "Maki Miyajima", "Shogo Ijima", "Koji Taniguchi", "Atsushi Niida", "Takako S Chikenji"], "journal": "Arthritis & rheumatology (Hoboken, N.J.)", "year": 2025, "abstract": "OBJECTIVE: This study investigates the role of senescent epidermal basal cells in cutaneous lupus erythematosus (CLE) pathogenesis using skin samples from patients with CLE and a mouse model of systemic lupus erythematosus (SLE).\nMETHODS: Cellular senescence profiling used datasets from the NCBI GEO database and Accelerating Medicines Partnership (AMP) Phase 1-Metro. Gene array data from GSE184989 (CLE, n = 68; control, n = 4), single-cell RNA sequencing data from GSE186476 (CLE, n = 7; control, n = 14), and AMP Phase 1-Metro (SLE, n = 17) were used. In vitro experiments further examined the expression of p21WAF1/CIP1, Type I interferon (IFN), HLA class I (HLA-I), and epidermal growth factor receptor (EGFR) signaling. Pharmacological clearance of senescent cells was performed using the senolytic drug fisetin in the SLE mouse model.\nRESULTS: p21WAF1/CIP1-high 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-I expression. In contrast, senescent epidermal cells up-regulate epidermal growth factor receptor signaling, which downregulates HLA-I expression, allowing them to evade immune surveillance. This heterogeneity of HLA-I expression promotes CD8-positive T-mediated toxicity against normal epidermal basal cells, resulting in their apoptosis. Pharmacological clearance of senescent epidermal basal cells improved SLE-like skin lesions.\nCONCLUSION: Senescent cells create a microenvironment that directs cytotoxic T cell-mediated 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.", "claims": [{"id": "claim-method", "statement": "To investigate cellular senescence in the skin tissue of patients with CLE, we performed Gene Set Enrichment Analysis (GSEA), 14 focusing on cellular senescence‐associated gene sets (SenMayo) 15 and hallmark gene sets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40386939", "locator": "sections[4] \"Cellular senescence‐associated factors are transcriptionally up‐regulated in skin tissues from patients with CLE\" paragraph 2", "quote": "To investigate cellular senescence in the skin tissue of patients with CLE, we performed Gene Set Enrichment Analysis (GSEA), 14 focusing on cellular senescence‐associated gene sets (SenMayo) 15 and hallmark gene sets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data supporting the findings of this study are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40386939", "locator": "sections[2] \"PATIENTS AND METHODS\" paragraph 2", "quote": "Data supporting the findings of this study are available from the corresponding author upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Senescent cells create a microenvironment that directs cytotoxic T cell-mediated responses against normal epidermis in patients with CLE, contributing to disease pathology.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40386939", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Senescent cells create a microenvironment that directs cytotoxic T cell‐mediated responses against normal epidermis in patients with CLE, contributing to disease pathology."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Senescent cells create a microenvironment that directs cytotoxic T cell-mediated responses against normal epidermis in patients with CLE, contributing to disease pathology.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40386939"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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