Scarring Hair Follicle Destruction Is Driven by the Collapse of EGFR-Protected JAK-STAT1-Sensitive Stem Cell Immune Privilege

This study reveals that the epidermal growth factor receptor (EGFR) plays a crucial role in protecting hair follicle stem cells from scarring degeneration by maintaining their immune privilege. When EGFR signaling is disrupted, it leads to increased sensitivity within the JAK-STAT1 pathway, which in turn compromises the immune privilege and makes the hair follicles susceptible to damage from CD8 T cells and NK cells. The researchers found that inhibiting JAK1/2 or depleting STAT1 genetically can restore immune privilege and stimulate hair growth in mouse models with EGFR deletion in the skin and hair follicles. Skin biopsies from patients treated with EGFR inhibitors and those with cicatricial alopecia (a type of scarring hair loss) showed active STAT1 signaling in the hair follicles. A case study of a patient with folliculitis decalvans, a condition causing progressive hair loss, scaling, and redness around hair follicles, showed successful treatment with systemic JAK1/2 inhibitors. These findings suggest a new therapeutic approach for treating hair follicle scarring caused by EGFR-inhibitor therapy and cicatricial alopecia.