The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index.
Comprehensive single-cell transcriptomic profiling of the scalp from patients with moderate-to-severe alopecia areata
Abstract
BACKGROUND Alopecia areata (AA) is an autoimmune hair loss disorder characterized by follicular destruction. While bulk transcriptomic studies have identified contributory inflammatory axes, specific cell pathways remain underexplored. OBJECTIVE To characterize the single-cell transcriptomic landscape underpinning AA scalp compared to healthy controls. METHODS We performed single-cell RNA-sequencing on lesional and nonlesional scalp biopsies from 13 patients with moderate-to-severe AA (5 with alopecia totalis/universalis [AT/AU]) and 11 healthy controls. RESULTS Overall, we profiled 41,067 high-quality cells. Lesional AA samples demonstrated robust Th1 activation and cytotoxicity, with upregulated IFNG, GZMH/K, and XCL1/2. Concurrently, Th2 skewing (IL13, IL13RA1, IL4R) and TNFRSF4/OX40 elevations in lesional CD4+ and regulatory T-cells were also observed. IL15, JAK2/3, and STAT1 levels were increased in distinct lesional dendritic cell subsets, with JAK/STAT genes also upregulated in fibroblasts and keratinocytes. Fibroblasts and smooth muscle cells exhibited enriched pro-inflammatory and pro-fibrotic markers (CXCL9, CCL26, POSTN, COL5A3, COL6A6). Lesional keratinocytes further demonstrated downregulated hair keratins and increased interferon signaling. AA endothelial cells showed increased angiogenic and interferon signatures. Compared to patchy AA and controls, AT/AU demonstrated higher expression of multiple cytotoxic, Th1, Th2, and JAK/STAT markers in immune cells, and proliferative and inflammatory signatures in non-immune cells. CONCLUSION This comprehensive high-resolution single-cell map uncovers potential communication networks between immune and non-immune cell populations in AA scalp, possibly disrupting immune privilege at the hair follicle and driving disease progression and/or severity.
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Metadata
- Authors
- Hu, B. D., He, H., Bose, S., Gour, D., Nandymazumdar, M., Zhou, J., Golla, A., del Duca, E., Beaziz, J., Avallone, G., Zhao, W., Pfeifer, H., DeGrange, M., Taliercio, M., Pasumarthi, A., Estrada, Y., & Guttman-Yassky, E.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2026-05
- Volume
- 157
- Issue
- 5
- Pages
- 1099-1113
- ISSN
- 0091-6749
- Cited by
- 5
- References
- 88
- Language
- en
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
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- Hu, B. D., He, H., Bose, S., Gour, D., Nandymazumdar, M., Zhou, J., Golla, A., del Duca, E., Beaziz, J., Avallone, G., Zhao, W., Pfeifer, H., DeGrange, M., Taliercio, M., Pasumarthi, A., Estrada, Y., & Guttman-Yassky, E. (2026). Comprehensive single-cell transcriptomic profiling of the scalp from patients with moderate-to-severe alopecia areata. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2026.02.014
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