Vitiligo is an autoimmune disease of the skin mediated by CD8 T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (T) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and mucosal-tropic viruses. Interleukin-15 (IL-15)-deficient mice reportedly have impaired T formation, and IL-15 promotes T function ex vivo. We found that both human and mouse T express the CD122 subunit of the IL-15 receptor and that keratinocytes up-regulate CD215, the subunit required to display the cytokine on their surface to promote activation of T cells. Targeting IL-15 signaling with an anti-CD122 antibody reverses disease in mice with established vitiligo. Short-term treatment with anti-CD122 inhibits T production of interferon-γ (IFNγ), and long-term treatment depletes T from skin lesions. Short-term treatment with anti-CD122 can provide durable repigmentation when administered either systemically or locally in the skin. On the basis of these data, we propose that targeting CD122 may be a highly effective and even durable treatment strategy for vitiligo and other tissue-specific autoimmune diseases involving T.

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Melasma is a common disorder of hyperpigmentation characterized by tan or brown macules and patches affecting sun-exposed areas, particularly the face. Melasma has been shown to have a significant impact on the quality of life and self-esteem of those affected. We interviewed six patients who were diagnosed with moderate-to-severe melasma with regard to the effect of their disorder on their self-esteem. All patients reported a significant negative effect on their quality of life and self-esteem. With successful therapy using a triple combination of cream and oral tranexamic acid to treat their melasma, all reported a marked improvement in self-esteem. Physicians who treat patients with melasma should be aware of its profound psychosocial effects and the improvement that successful melasma treatment can have on self-esteem.

scRNA-seq of human vitiligo samples reveals complex autoimmune networks, including a role for CCR5 in T reg function.