ABSTRACT Early intervention is essential for a successful therapy and a favorable prognosis in vitiligo treatment. While emerging evidence indicates an association between the type I interferons (I‐IFNs) signature and the initiation of the immune response, it remains unclear whether I‐IFNs function as a critical mediator in the vitiligo initiation phase. Their precise molecular mechanisms of action necessitate further investigation. I‐IFNs mainly include subtypes IFNα, IFNβ, and IFNκ. In our study, we observed markedly elevated levels of IFNβ in both peripheral blood and perilesional skin of vitiligo patients. Then, employing multiple vitiligo models and IFNAR‐deficient mice, we proved that IFNβ signaling through the IFNAR1/IFNAR2 receptor is critically required for disease initiation. Mechanically, IFNβ directly induced melanocyte apoptosis. In addition, it specifically induced melanocytes, but not keratinocytes, to secrete the chemokines CXCL9/10/11. These chemokines subsequently recruited cytotoxic CD8 + T cells to the epidermis, amplifying the immune response and ultimately leading to melanocyte destruction. Finally, intervention with triptolide—a potent IFNβ inhibitor derived from the medicinal plant Tripterygium wilfordii —confirmed that suppressing IFNβ signaling can inhibit the initiation of vitiligo.
Wang et al. (Sat,) studied this question.