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.

BACKGROUND Vitiligo is an autoimmune disease wherein cutaneous depigmentation occurs. Existing therapies are often inadequate. Prior reports have shown benefit of the Janus kinase (JAK) inhibitors. OBJECTIVE To evaluate the efficacy of the JAK 1/3 inhibitor, tofacitinib, in the treatment of vitiligo. METHODS This is a retrospective case series of 10 consecutive patients with vitiligo treated with tofacitinib. Severity of disease was assessed by body surface area of depigmentation. RESULTS Ten consecutive patients were treated with tofacitinib. Five patients achieved some repigmentation at sites of either sunlight exposure or low-dose nbUVB. Suction blister sampling revealed that the autoimmune response was inhibited during treatment in both responding and non-responding lesions, suggesting that light was primarily required for melanocyte regeneration, rather than immunosuppression. LIMITATIONS Limitations include the small size, retrospective nature, and lack of a control group. CONCLUSION Treatment of vitiligo with JAK inhibitors appears to require light exposure. In contrast to treatment with phototherapy alone, repigmentation during treatment with JAK inhibitors may require only low-level light. Maintenance of repigmentation may be achieved with JAK inhibitor monotherapy. These results support a model wherein JAK inhibitors suppress T cell mediators of vitiligo and light exposure is necessary for stimulation of melanocyte regeneration.

Lung dendritic cells promote lung homing by T cells in part via up-regulation of chemokine receptor CCR4.

Background Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies. Objective To investigate potential markers of disease activity directly in the skin of vitiligo subjects and healthy subjects. Methods Patient skin was sampled via a modified suction blister technique allowing for minimally invasive, objective assessment of cytokines and T cell infiltrates in interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups. Results In screening and validation, CD8+ T cell number and CXCL9 protein concentration were significantly elevated in active lesional compared to non-lesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by ROC analysis. Suction blistering also allowed for phenotyping of the T cell infiltrate, which overwhelmingly expresses CXCR3. Limitations A small number of patients were enrolled for the study, including a single patient to define the treatment response. Conclusion Measuring CXCL9 directly in the skin may be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.