{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:11:48Z","timestamp":1778739108932,"version":"3.51.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vitiligo is a chronic inflammatory skin disease characterized by clinical and molecular heterogeneity across lesional, perilesional and non-lesional skin within the same individual. Understanding these region-specific differences is essential for identifying early disease processes and developing targeted therapeutic strategies. Skin biopsies represent a key approach to explore these differences, yet conventional 3\u20135 mm biopsies are invasive, requiring sutures, extended healing time and leaving visible scarring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The objective of this study was to characterize region-specific transcriptomic alterations across lesional, perilesional, and non-lesional skin in vitiligo, using minimally invasive 1\u00a0mm skin punch biopsies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, bulk RNA sequencing was performed on 105 skin biopsies obtained from perilesional and (non-)lesional skin of non-segmental vitiligo patients, as well as healthy control skin. Differential gene expression was followed by pathway-level analyses, and Connectivity Map\u2013based perturbational profiling was performed to predict candidate therapeutic compounds capable of reversing the lesional transcriptional signature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Transcriptomic profiling of 1\u00a0mm biopsies revealed disease-associated changes across lesional, perilesional, and non-lesional vitiligo skin, with distinct region-specific gene signatures reflecting immune activation and metabolic reprogramming. Pathway analysis further identified dysregulation of both canonical and underexplored pathways, including NOD-like receptor signaling and neutrophil extracellular trap formation, alongside altered cellular clearance mechanisms potentially implicated in lesion persistence. Connectivity Map analysis nominated compounds predicted to reverse the lesional transcriptional signature, spanning epigenetic regulators, tyrosine kinase inhibitors, and metabolic modulators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This approach uncovers potentially pathogenic pathways contributing to vitiligo pathogenesis and provides a translational framework for therapeutic hypothesis generation and future clinical studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1829996","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:33:10Z","timestamp":1778736790000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Minimally invasive 1\u00a0mm skin biopsies capture site-specific transcriptomic heterogeneity in 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