Identification of BST2 as a biomarker for alopecia areata in both mice and humans

Abstract Alopecia areata is an autoimmune disease characterized by aberrant non-scarring hair loss. 147 million people worldwide are currently diagnosed with alopecia areata with a lifetime incidence of 2.1%. The hair follicle is a site of immune privilege however in alopecia areata, CD4+ helper T cells and CD8+ cytotoxic T cells infiltrate and attack the hair follicle. To better understand the initiating mechanisms surrounding alopecia areata, we examined the function of epidermal γδ T cells and dermal macrophages in the initiation of or protection from the disease. We show that epidermal γδ T cells and keratinocytes are elevated in the skin of C3H/HeJ mice with alopecia areata. Analysis of publicly available single cell RNA sequencing data delineated the top differentially expressed genes of epidermal γδ T cells and dermal macrophages. Bone marrow stromal antigen 2 (BST2) is significantly upregulated among both cell types and is a novel gene associated with alopecia areata. Using immunofluorescence microscopy we determined that a small population of hair follicle-associated epidermal γδ T cells express BST2 in C3H/HeJ mice and C57Bl/6J mice without alopecia areata. We have also identified a significant increase in BST2 expression in skin sections from mice affected by alopecia areata. BST2+CD11b+ macrophages upregulate genes associated with antiviral activity indicating an association between the pathogenesis of alopecia areata and infectious viral particles. BST2+ epidermal γδ T cells upregulate genes associated with FAK signaling in alopecia areata, which indicates a role for FAK in the increased number of epidermal T cells. These studies identify a role for BST2 in alopecia areata that is mediated by epidermal γδ T cells and macrophages.