{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:58:05Z","timestamp":1792627085081,"version":"4.5.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Plan Propio de Investigaci\u00f3n del Instituto Maim\u00f3nides de Investigaci\u00f3n Cl\u00ednica"},{"name":"International Eczema Council"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Nonsegmental vitiligo (NSV) is an autoimmune condition characterized by melanocyte loss. While skin-specific mechanisms have been well studied, systemic immune dysregulation contributing to NSV pathogenesis remains unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To use a multi-omic single-cell approach to investigate circulating immune cells in NSV, integrating transcriptional and chromatin accessibility data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>An integrative single-cell RNA sequencing (scRNAseq)\/single-cell assay for transposase-accessible chromatin sequencing (scATACseq) analysis was conducted on peripheral blood mononuclear cells (PBMCs) from people with NSV (n = 11) and healthy control participants (n = 5), identifying transcriptional markers, cell\u2013cell interactions, chromatin accessibility and transcription factor (TF) dynamics. Key findings were validated in an expanded cohort (patients with NSV, n = 16; healthy controls, n = 9) using spectral flow cytometry, with additional stratification by sex, age, disease activity, severity and duration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Analysis of 59 192 PBMCs identified 8204 gene expression markers and 13 925 ATAC peaks across 25 immune cell subtypes. A broadly activated immune response was observed, characterized by cytotoxicity, antigen presentation, cell exhaustion and stress, predominantly in monocytes, natural killer cells, CD8+ T cells and dendritic cells. Multi-omic integration revealed T helper (Th)1\/Th17 polarization and dysfunctional regulatory T cell [Treg\/memory Treg (mTreg)] responses. Chromatin accessibility highlighted enriched TF binding sites for forkhead box O3 (FOXO3), Sp1, activator protein 1 (AP-1), signal transducer and activator of transcription (STAT)1\/STAT3, interferon regulatory factor (IRF)1 and IRF4, regulating pathways linked to cytotoxicity, antigen processing, nuclear factor-\u03baB, Toll-like receptor and Janus kinase\/STAT signalling. Flow cytometry validated these findings, showing that disease activity and shorter duration were associated with heightened immune dysregulation. Robust T-cell receptor activation drove Th1\/Th17 polarization and elevated interferon-\u03b3 and tumour necrosis factor-\u03b1 production in CD4+ and CD8+ T cells. Cutaneous lymphocyte-associated antigen (CLA)+ skin-homing Th1\/Th17-polarized CD4+ T cells, CD8+ T cells and mTregs exhibited persistent activation, marked by basal programmed cell death protein 1 (PD1)+ expression. OX40\/OX40L-mediated interactions between monocytes and effector T cells amplified inflammation. Regulatory dysfunction, including reduced interleukin (IL)-4 and IL-13 production by mTregs, was prominent in moderate-to-severe and active disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This is the first multi-omic single-cell study of PBMCs from people with NSV, revealing systemic immune dysregulation driven by cytotoxicity, antigen presentation, exhaustion and regulatory failure. Disease severity, activity and evolution influence these pathways, highlighting the OX40\/OX40L axis as a potential therapeutic target to mitigate immune dysregulation and relapse risk.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljaf041","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T20:32:26Z","timestamp":1738269146000},"page":"115-124","source":"Crossref","is-referenced-by-count":21,"title":["Comprehensive single-cell chromatin and transcriptomic profiling of peripheral immune cells in nonsegmental vitiligo"],"prefix":"10.1093","volume":"193","author":[{"given":"Jesus","family":"Gay-Mimbrera","sequence":"first","affiliation":[{"name":"Inflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)\/University of Cordoba\/Reina Sofia University Hospital , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lozano-Ojalvo","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai Hospital , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro J","family":"G\u00f3mez-Arias","sequence":"additional","affiliation":[{"name":"Inflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)\/University of Cordoba\/Reina Sofia University Hospital , C\u00f3rdoba ,","place":["Spain"]},{"name":"Department of Dermatology, Reina Sof\u00eda University Hospital , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Rivera-Ruiz","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Reina Sof\u00eda University Hospital , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Aguilar-Luque","sequence":"additional","affiliation":[{"name":"Inflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)\/University of Cordoba\/Reina Sofia University Hospital , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Moch\u00f3n-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Inflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)\/University of Cordoba\/Reina Sofia University Hospital , C\u00f3rdoba ,","place":["Spain"]},{"name":"Department of Dermatology, Reina Sof\u00eda University Hospital , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elo\u00edsa","family":"And\u00fajar Pulido","sequence":"additional","affiliation":[{"name":"Genomic Unit, Andalusian Molecular Biology and Regenerative Medicine Center (CABIMER), CSIC \u2013 University of Seville \u2013 University Pablo de Olavide , Seville ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"P\u00e9rez-Alegre","sequence":"additional","affiliation":[{"name":"Genomic Unit, Andalusian Molecular Biology and Regenerative Medicine Center (CABIMER), CSIC \u2013 University of Seville \u2013 University Pablo de Olavide , Seville ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Guttman-Yassky","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai Hospital , New York, NY 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