A transcriptomic atlas of murine and human alopecia areata identifies immune cell profiles predictive of human disease state.

Alopecia areata (AA) is one of the most common autoimmune conditions, presenting initially with loss of hair without overt skin changes. The unremarkable appearance of the skin surface contrasts with the complex immune activity occurring at the hair follicle. AA pathogenesis is due to the loss of immune privilege of the hair follicle leading to autoimmune attack. Although the literature has focused on CD8+ T cells, vital roles for CD4+ T cells and antigen-presenting cells have been suggested. Here, we use single-cell sequencing to reveal distinct expression profiles of immune cells in AA. We found clonal expansions of both CD4+ and CD8+ T cells, with shared clonotypes across varied transcriptional states. These data were used to generate highly predictive models of human AA disease. Finally, single-cell sequencing of T cells in human AA recapitulated the clonotypic findings and the gene expression of the predictive models. CD45+ immune cells were isolated from skin and lymph nodes of mice with AA and control, while in humans CD45+ T cells were isolated from AA skin. Single-cell suspensions were processed with the Chromium Single Cell 5-prime Library & Gel Bead Kit and the 10x Genomics TCR Immunprofiling kit.