Hair follicle stem cells and the collapse of self-tolerance in alopecia: the interplay of barrier function, the microbiome, and immunity.

The hair follicle is thought to be a site of ‘immune privilege,’ or relative protection from autoimmune and inflammatory responses. In particular, the long-lived, quiescent hair follicle stem cells (HFSCs) are strikingly resistant to cytotoxic immune effectors such as T cells and natural killer (NK) cells, even in systems where these cells are artificially directed to attack HFSCs. Nonetheless, many forms of alopecia are associated with immune-mediated damage of the hair follicle epithelium, suggesting a failure of immune privilege. What precipitates the collapse of HFSC immune privilege in alopecia? In this current issue of , Strobl et al use an innovative mouse model to add to our mechanistic understanding of this disorder (Strobl et al, 2024).