{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:16:58Z","timestamp":1791389818500,"version":"4.3.3"},"reference-count":44,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lichen sclerosus (LS) is a chronic inflammatory skin disorder with an incompletely understood molecular pathogenesis. This systematic review aimed to synthesize current evidence on key molecular mechanisms underlying the disease, with a particular focus on immune dysregulation, epigenetic modifications, and tissue remodeling. A structured literature search identified studies employing transcriptomic, epigenetic, and experimental approaches. The strongest evidence consistently supports a central role of immune activation, particularly T cell-mediated responses involving Th1- and Th17-related pathways, accompanied by increased expression of pro-inflammatory cytokines and activation of the NF-\u03baB signaling pathway. Epigenetic and post-transcriptional mechanisms, including dysregulated microRNAs (notably miR-155-5p) and altered DNA methylation patterns, may sustain immune imbalance and fibroblast activation partly via modulation of the FOXO signaling pathway. In parallel, experimental and multi-omics studies highlight enhanced fibroblast activity and extracellular matrix remodeling, largely associated with the TGF-\u03b2 signaling pathway, linking inflammation with progressive fibrosis. Emerging data also suggest interactions between immune signaling and metabolic alterations, although these findings remain preliminary. Overall, the available evidence indicates that LS may involve a complex interplay between immune, epigenetic, and fibrotic mechanisms. While several molecular pathways and candidate biomarkers have been identified, their clinical relevance requires further validation in larger, well-designed studies.<\/jats:p>","DOI":"10.3390\/ijms27135968","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T07:59:47Z","timestamp":1783065587000},"page":"5968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Mechanisms in the Etiopathology of Lichen Sclerosus: A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4219-5676","authenticated-orcid":false,"given":"Katarzyna","family":"Beutler","sequence":"first","affiliation":[{"name":"University Centre of General Dermatology and Oncodermatology, Faculty of Medicine, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofiia","family":"Khimuk","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9331-7342","authenticated-orcid":false,"given":"Anastazja","family":"Andrusiewicz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Mutwicki","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariya","family":"Pozdnyakova","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1717-4280","authenticated-orcid":false,"given":"Danuta","family":"Nowicka","sequence":"additional","affiliation":[{"name":"University Centre of General Dermatology and Oncodermatology, Faculty of Medicine, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.25259\/CSDM_225_2024","article-title":"A concise history of the contributions of Francois Henri Hallopeau (1842\u20131919): Serendipity in dermatology","volume":"5","author":"Sekar","year":"2025","journal-title":"Cosmoderma"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1600-0560.1976.tb01105.x","article-title":"New Nomenclature for Vulvar Disease","volume":"3","author":"Kaufman","year":"1976","journal-title":"J. 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