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 TYK2 inhibitor, BMS-986202, to prevent and reverse hair follicle immune privilege collapse in a humanized mouse model. The treatment reduced MHC-I/II expression, inhibited keratinocyte apoptosis, and promoted hair regrowth by restoring immune privilege. The findings suggest that IL-12 signaling is crucial in AA pathogenesis by stimulating IFNγ production, leading to immune privilege collapse. Thus, inhibiting TYK2-dependent IL-12 signaling could be a promising treatment strategy for AA.