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  • Writer's pictureCure Vitiligo

Antibody Blockade of IL-15 Signaling has the Potential to Durably Reverse Vitiligo

This is a summarized version of the study conducted by the Department of Dermatology at the University of Massachusetts Medical School.

Vitiligo is an autoimmune disease of the skin that kills melanocytes and creates white spots. Lesional T cells in mice and humans with vitiligo display a resident memory (TRM) phenotype. Short-term treatment with anti-CD122 can provide durable repigmentation in the skin, scientists say. They propose that targeting CD122 may be a highly effective and even durable treatment strategy for Vitiligo and other tissue-specific autoimmune diseases involving TRM.

Depigmentation typically recurs rapidly at the same location after therapy is stopped. This indicates that autoimmune memory persists in the skin and permits disease reactivation. The presence of resident memory T cells (TRM) in vitiligo has now been reported by several laboratories. It has been difficult to implicate them directly as necessary and/or sufficient for the disease because of the lack of tools available to remove them.

Previous studies in mice have shown that interleukin-15 (IL-15) is important for the generation of TRM in viral infections and in cutaneous lymphomas. It has been proposed that targeting IL-15 might be useful for the treatment of autoimmune diseases. Here, we first confirmed that human and mouse TRM are present in lesional skin and that they express components of the IL-15 receptors. We found that melanocyte-specific T cells express the CD122 subunit, whereas keratinocytes express CD215, consistent with an ability to present IL-15 to T cells in trans.

We tested whether blockade of CD122 signaling with a monoclonal antibody could serve as a treatment for vitiligo. Long-term CD122 blockade depleted PMEL TRM from the skin, and short-term blockade reduced effector function. Our data suggest that targeted treatment of IL-15 signaling may provide a novel, durable treatment strategy for vitiligo and other organ-specific autoimmune diseases.

We believe that T cells are recruited to the skin via the CXCR3 chemokine axis, encounter IL-15 presented in trans on keratinocytes, up-regulate IFN gamma at the dermal-epidermal junction, and become dependent on IL- 15 for their survival. We treated mice with established vitiligo with anti-CD122 intradermally for 4 weeks, then stopped the treatment, and observed repigmentation over a 10-week period. These data suggest that targeting IL-15 in vitiligo, unlike existing therapies, could provide a durable treatment option for patients.


(A) Timing of treatments in the efficacy/repigmentation model. i.v., intravenous; i.p., intraperitoneal. (B) Sample photos of vehicle control [phosphate-buffered saline (PBS) or isotype] and anti-CD122 antibody (Ab)-treated animals at treatment baseline and week 8. (C) Comparison of the final percent change in pigmentation in vehicle and anti-CD122 antibody-treated animals. (D) Quantification of PMEL numbers in treated animals within the indicated tissues. (E) Quantification of host CD8+ T cell numbers in treated animals within the indicated tissues (each dot represents one animal; pooled from two separate experiments, n = 11 vehicle mice and n = 11 anti-CD122 antibody-treated mice; t tests significant as indicated). LN, lymph node.

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