Single-Cell Analysis of Temporal Immune Cell Dynamics in Alopecia Areata Reveals a Causal Role for Clonally Expanded CD8+ T Cells in Disease

This study investigates the role of clonally expanded CD8⁺ T cells in the pathogenesis of alopecia areata (AA) using the C3H/HeJ mouse model. Through single-cell RNA and T cell receptor (TCR) sequencing, researchers identified a significant hyper-expansion of T cell clones linked to disease onset. By engineering TCR retrogenic mice and applying CRISPR-Cas9 to modify TCR sequences within CD8⁺ T cells, they demonstrated that these expanded T cell clones are sufficient to initiate AA. The findings establish a causal relationship between CD8⁺ T cell clonality and the pathogenicity of AA, highlighting the critical role of these immune cells in the disease.