{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T01:35:44Z","timestamp":1789263344262,"version":"build-2803163510"},"reference-count":87,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss ranging from mild, self-limiting episodes to severe and chronic forms. While prior research has primarily focused on lesional skin, the contribution of systemic immune cells remains underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) from patients with mild and severe AA, as well as healthy controls. A total of 32,453 high-quality cells were analyzed across 36 immune cell subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In AA patients, especially those with severe disease, we observed increased transcriptional heterogeneity, cytokine and chemokine pathway activation, and upregulation of antigen-presentation machinery enriched in TH1, TH2, and TH17 signatures. Chromatin accessibility profiling revealed 42,248 significant peaks with pronounced epigenetic remodeling in\n                      <jats:italic>CD14<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      monocytes, NK cells, and\n                      <jats:italic>CD8<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Mild AA showed early immune regulatory failure, with elevated exhaustion markers in double-negative T cells and increased apoptosis in myeloid populations. Pseudotime and transcription factor analyses indicated altered differentiation trajectories, and inferred cell-cell communication networks highlighted monocytes, NK cells, and memory T cells as key signaling hubs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our results provide the first integrated single-cell chromatin and transcriptomic map of peripheral immune dysregulation in AA. These findings uncover systemic alterations associated with disease severity and identify candidate pathways for immune modulation and therapeutic targeting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1565241","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T01:52:44Z","timestamp":1751421164000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata"],"prefix":"10.3389","volume":"16","author":[{"given":"Jesus","family":"Gay-Mimbrera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro 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