Tyrosine Kinase 2 Inhibition Rescues Hair Follicles From IL-12-Mediated Immune Privilege Collapse And Reverses Human Alopecia Areata In A Humanized Mouse Model

The study investigates the role of IL-12 and TYK2-mediated signaling in alopecia areata (AA), an immune-mediated hair loss disorder. Researchers used a selective TYK2 inhibitor, BMS-986202, to explore its effects on hair follicle immune privilege (IP) collapse. In human scalp hair follicle organ culture, IL-12+IL-18 treatment increased immune activity and IFNγ-inducible gene expression, leading to IP collapse. BMS-986202 treatment prevented and reversed these effects, indicating that IL-12 receptor signaling is crucial for IP collapse. In a humanized AA mouse model, BMS-986202 restored hair follicle IP, reduced immune markers, inhibited keratinocyte apoptosis, and promoted hair regrowth. The findings suggest that inhibiting TYK2-dependent IL-12 signaling could be a potential treatment strategy for AA.