Targeting the IL-15/CD122 signaling pathway: reversing TRM cell-mediated immune memory in vitiligo

Vitiligo is a chronic autoimmune disorder in which melanocyte-specific CD8⁺ T cells destroy pigment-forming cells, producing persistent depigmented macules. Recurrence after treatment implicates tissue-resident memory T (TRM) cells that are maintained by interleukin-15 (IL-15) signaling. Here we review current insights into TRM-cell biology, summarize experimental and emerging clinical data targeting the IL-15/CD122 axis-including the ongoing Phase 2a AMG 714 trial-and discuss combination strategies with approved topical Janus kinase inhibitors such as ruxolitinib cream. Disrupting IL-15 may offer durable repigmentation with minimal systemic immunosuppression.