{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:07:09Z","timestamp":1790885229537,"version":"4.1.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alopecia areata (AA) is an autoimmune hair loss disorder. Although autoreactive CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells are central effectors, the roles of stromal and epithelial compartments in sustaining inflammation remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study analyzed publicly available scRNA-seq data from the GEO database (GSE212450, GSE233906), comprising 15 scalp samples from normal skin (NS), non-lesional (NL), and AA conditions. Following integration, normalization, and clustering, cells were annotated using established marker genes. Subclustering focused on immune, epithelial, and fibroblast lineages. Differential expression and enrichment analyses identified disease-associated genes and pathways. CellChat was used to compare ligand\u2013receptor interactions and signaling networks between NS and AA microenvironments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      scRNA-seq analysis revealed a profoundly remodeled immune niche in AA lesions, extending beyond immune cells to encompass epithelial cells and fibroblasts. Key features included lymphoid-myeloid expansion, clonal cytotoxic CD8\n                      <jats:sup>+<\/jats:sup>\n                      T1 cell accumulation, mast cell loss, and elevated DC3-derived IL-15. Epithelial cells exhibited upregulated MHC-II and immunomodulatory activity despite stable proportions. A novel pro-inflammatory fibroblast subset (FB3), enriched in AA, expressed high levels of MIF, displayed inflammatory and stress-related signatures, and suppressed extracellular matrix organization. Ligand-receptor analysis identified an intensified MIF-centered inflammatory circuit, primarily via MIF-(CD74\u202f+\u202fCXCR4\/CD44) axes, forming a robust signaling network connecting FB3 and multiple dendritic cell subsets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals that fibroblasts in AA lesions, particularly the newly identified FB3 subset, are not merely passive structural cells but rather active participants in immune-inflammatory regulation through the elevated secretion of MIF. The enhanced MIF-(CD74\u202f+\u202fCXCR4\/CD44) signaling axis constitutes a core mechanism connecting FB3 cells with multiple dendritic cell subsets. This finding suggests that targeting FB3 differentiation or inhibiting MIF-related signaling pathways may represent a promising therapeutic avenue for AA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1849368","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:58:16Z","timestamp":1779425896000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Single-cell landscape of immune remodeling in alopecia areata suggests MIF\u202f+\u202ffibroblasts and their potential ligand-receptor crosstalk with dendritic cells"],"prefix":"10.3389","volume":"13","author":[{"given":"Xuemei","family":"Lan","sequence":"first","affiliation":[{"name":"Department of Dermatology, Zigong Fourth People\u2019s Hospital","place":["Zigong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunting","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Zigong Fourth People\u2019s Hospital","place":["Zigong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1111\/exd.14155","article-title":"Hair follicle immune privilege and its collapse in alopecia areata","volume":"29","author":"Bertolini","year":"2020","journal-title":"Exp 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