Ultraviolet radiation as a double-edged regulator of melanocyte function in vitiligo therapy and melanoma...

Vitiligo is a chronic autoimmune disorder characterized by selective melanocyte loss and progressive depigmentation. Narrowband ultraviolet B (NB-UVB) and excimer-based phototherapy are widely regarded as standard treatments in clinical practice and remain the most effective approaches for inducing repigmentation. However, excessive or uncontrolled ultraviolet radiation (UVR) exposure can impair skin barrier function, cause melanocyte dysfunction, and increase the risk of photoaging and carcinogenesis. This apparent paradox arises from the bidirectional biological effects of UVR: on the one hand, UVR activates melanocytes and promotes skin pigmentation through coordinated effects on melanocyte maturation, proliferation, and melanin synthesis, while on the other hand, UVR can induce oxidative stress, DNA damage, apoptosis, and genomic instability. Therefore, combination strategies incorporating JAK inhibitors, platelet-rich plasma, or cellular grafting techniques have been increasingly explored in clinical practice. In this review, we provide an integrated perspective on the dual effects of UVR on melanocyte biology, discuss emerging combination therapies for vitiligo, and highlight the mechanistic links between phototherapy, melanocyte homeostasis, and melanoma risk.