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

Front Immunol. 2025 Jul 28:16:1639732. doi: 10.3389/fimmu.2025.1639732. eCollection 2025.

Abstract

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.

Keywords: AMG 714; CD122; IL-15; ruxolitinib; tissue-resident memory T cell; vitiligo.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immunologic Memory*
  • Interleukin-15* / immunology
  • Interleukin-2 Receptor beta Subunit* / immunology
  • Janus Kinase Inhibitors / therapeutic use
  • Memory T Cells* / immunology
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • Signal Transduction
  • Vitiligo* / drug therapy
  • Vitiligo* / immunology

Substances

  • IL15 protein, human
  • Interleukin-15
  • IL2RB protein, human
  • Interleukin-2 Receptor beta Subunit
  • ruxolitinib
  • Janus Kinase Inhibitors
  • Nitriles
  • Pyrazoles
  • Pyrimidines