Comprehensive single-cell transcriptomic profiling of the scalp from patients with moderate-to-severe alopecia areata - 05/05/26
, Swaroop Bose, MS, Digpal Gour, PhD, Monali Nandymazumdar, PhD, Jerry Zhou, MS, Anudeep Golla, BS, Ester del Duca, MD, PhD, Jessica Beaziz, MD, Gianluca Avallone, MD, William Zhao, MD, PhD, Hailey Pfeifer, MD, Madeleine DeGrange, MD, Mark Taliercio, MD, Anusha Pasumarthi, MD, Yeriel Estrada, BS, Emma Guttman-Yassky, MD, PhD ⁎ 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 |
We characterized the single-cell transcriptomic landscape underpinning AA scalp compared to healthy controls.
Methods |
We performed single-cell RNA sequencing on lesional (LS) and nonlesional scalp biopsy samples from 13 patients with moderate-to-severe AA (5 with alopecia totalis/universalis) and 11 healthy controls.
Results |
Overall, we profiled 41,067 high-quality cells. LS AA samples demonstrated robust T H 1 activation and cytotoxicity, with upregulated IFNG, GZMH/K, and XCL1/2 . Concurrently, T H 2 skewing (IL13, IL13RA1, IL4R) and TNFRSF4 /OX40 elevations in LS CD4 + and regulatory T-cells were also observed. IL15, JAK2/3, and STAT1 levels were increased in distinct LS dendritic cell subsets, with JAK/STAT genes also upregulated in fibroblasts and keratinocytes. Fibroblasts and smooth muscle cells exhibited enriched proinflammatory and profibrotic markers (CXCL9, CCL26, POSTN, COL5A3, COL6A6). LS 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, alopecia totalis/universalis demonstrated higher expression of multiple cytotoxic, T H 1, T H 2, and JAK/STAT markers in immune cells, and proliferative and inflammatory signatures in nonimmune cells.
Conclusion |
This comprehensive high-resolution single-cell map uncovers potential communication networks between immune and nonimmune cell populations in AA scalp, possibly disrupting immune privilege at the hair follicle and driving disease progression and/or severity.
Le texte complet de cet article est disponible en PDF.Key words : Alopecia areata, dendritic cells, fibroblasts, immune privilege, immunology, keratinocytes, single-cell RNA-Seq, smooth muscle cells, T-cells, transcriptomics
Abbreviations used : AA, AD, AT, AU, CCL, cDC1/2, CXCL, DC, DEG, ECM, FB, HC, IP, JAK, KC, LC, LS, MACDC, NL, pAA, scRNA-Seq, SMC, STAT, TC, Tc1, TNFRSF4, VEC
Plan
| The first 2 authors contributed equally to this article, and both should be considered first author. |
Vol 157 - N° 5
P. 1099-1113 - mai 2026 Retour au numéro
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