Preclinical Evidence Supporting Selective Inhibition of Tyrosine Kinase 2-Dependent, IL-12-Mediated Signaling as a Novel Strategy for Alopecia Areata Management

The study investigates the role of interleukin (IL)-12 in the collapse of hair follicle immune privilege (HF-IP), a key factor in alopecia areata (AA), a hair loss disorder. The researchers found that stimulating healthy human hair follicles with IL-12/IL-18 led to an expansion of T and natural killer cells and an IFNγ-dependent IP collapse. This collapse was prevented by inhibiting IL-12 signaling with the tyrosine kinase-2 (TYK2) inhibitor, BMS-986202. The study also found more IL-12RB2+ cells around the bulb of acute AA lesional scalp skin compared to healthy samples. Treatment of acute AA scalp biopsies with BMS-986202 promoted anagen in non-lesional and lesional hair follicles and rescued IP collapse in lesional hair follicles. It also reduced the number of infiltrating CD3+ T cells in the hair follicle epithelium and perifollicular mesenchyme of lesional hair follicles from acute and chronic AA scalp. The study concludes that TYK2 inhibition is a promising pharmacological strategy for managing AA.