Single-cell Transcriptomics of Human Alopecia Areata Reveals Clonally Expanded and Activated CD4+ and CD8+ T-cell Populations

Alopecia areata (AA) is a common autoimmune disease that causes hair loss from the scalp and body. Treatment of AA with intralesional and systemic immunosuppressants is limited by incomplete clinical responses and sequelae associated with chronic immunosuppression, highlighting the need for new targeted treatments. CD4+ and CD8+ T-cells are known mediators of AA, however the cellular states of autoreactive disease driving T-cells is not well understood. Here, we use paired single-cell RNA and T-cell receptor sequencing to profile cutaneous T-cells of AA and healthy controls. Compared to healthy subjects, we find that active lesions of AA contain enriched populations of CD4+ and CD8+ T-cells that are clonally expanded, express markers associated with chronic antigenic stimulation, and display an inflammatory Th1 phenotype. Bioinformatic clustering of T-cell receptor sequences revealed shared clonotypes unique to AA patients that represent putative autoreactive receptors. Overall, our data identifies pathogenic T-cell populations and clonotypes associated with alopecia areata and immune mechanisms leading to disease pathogenesis.