Comprehensive Single-Cell Transcriptomic Profiling of the Scalp from Patients with Moderate-to-Severe Alopecia Areata

This study conducted single-cell RNA sequencing on scalp biopsy samples from 13 patients with moderate-to-severe alopecia areata (AA) and 11 healthy controls, profiling 41,067 high-quality cells. It revealed significant TH1 activation, cytotoxicity, and TH2 skewing in AA samples, with upregulated genes such as IFNG and JAK/STAT pathways. The study highlights potential communication networks between immune and nonimmune cells that may disrupt immune privilege at the hair follicle, contributing to disease progression. It identifies key gene-regulatory programs and critical cell types, such as Arg1+ macrophages and specific T-cell populations, involved in AA pathogenesis, suggesting that impaired autophagy and systemic immune dysregulation contribute to hair loss. This research enhances the understanding of molecular mechanisms underlying AA and may inform future therapeutic strategies.