Tyrosine Kinase 2 Inhibition Ameliorates the Phenotype of Lesional Alopecia Areata Scalp Skin Ex Vivo, and Reverses the Induction of Human Alopecia Areata in a Humanized Mouse Model

The study investigates the role of Tyrosine Kinase 2 (TYK2) inhibition in the treatment of Alopecia Areata (AA), an immune-mediated hair follicle disorder. Using the TYK2 inhibitor BMS-986202 (BMS), researchers treated human scalp skin biopsies from AA patients and a humanized mouse model. BMS treatment prolonged the anagen phase in hair follicles, reduced MHC I and II expression, and decreased the number of CD3+ T cells in lesional scalp biopsies. In the mouse model, BMS and tofacitinib increased hair shaft numbers, reduced keratinocyte apoptosis, and decreased immune cell infiltration. These findings suggest that TYK2 inhibition could be a promising pharmacological strategy for managing AA, warranting further clinical exploration.