Researchers have found that targeting the activity of a class of T cells restores pigmentation of the skin in a mouse model of vitiligo. Their discovery could lay the foundation for new vitiligo therapies that achieve more durable and long-lasting results compared to current treatment methods. Vitiligo is an autoimmune disorder that develops when T cells attack and destroy skin cells that produce the dark pigment melanin, resulting in a loss of skin color and the appearance of white spots. The condition affects approximately 1% of the population worldwide, or around 75 million people, and can cause distress and anxiety in patients. Scientists have developed treatments for vitiligo that can temporarily restore pigmentation and color in affected skin patches, but depigmentation returns in up to 40% of cases within the first year after treatment is completed. Researchers have hypothesized this recurrence could be due to the actions of a type of T cell named resident memory T cells (or TRMs). However, translating these findings into a more durable treatment for vitiligo has proved difficult. In this study, Jillian Richmond and colleagues analyzed lesions from vitiligo patients and found they contained TRMs that express components of a receptor for interleukin-15 (IL-15), an immune signaling molecule; TRMs from a mouse model of vitiligo displayed the same IL-15 receptor. They then administered an antibody that targets the IL-15 receptor for two weeks to mice with established vitiligo, and observed the treatment restored pigmentation in the mice over the next two months. The authors will conduct clinical trials in the near future to determine whether targeting TRMs could represent a viable therapeutic strategy for vitiligo patients.