Single-Cell Protein Activity Inference Analysis of Full-Thickness Skin Uncovers Novel Pathways and a Rare Arg1+ Macrophage Population in Alopecia Areata

This study investigated the cellular landscape of Alopecia Areata (AA) skin using single-cell RNA sequencing of full-thickness dorsal skin from C3H/HeJ mice. The research identified a keratinocyte-specific MHC Class II signature and highlighted necroptosis as a hair follicle-intrinsic immunogenic mechanism in AA. A novel population of Arg1+ macrophages was discovered, which showed upregulation of arginine metabolism genes and pro-inflammatory cytokines. The administration of the arginase inhibitor nor-NOHA delayed the onset of AA in mice, suggesting a pathogenic role for Arg1+ macrophages. These findings demonstrated the potential of inferred single-cell protein activity to identify new therapeutic targets in AA.