The IFN-γ-CXCL9/CXCL10-CXCR3 axis in vitiligo: Pathological mechanism and treatment

Eur J Immunol. 2024 Apr;54(4):e2250281. doi: 10.1002/eji.202250281. Epub 2024 Mar 5.

Abstract

Vitiligo is a disease featuring distinct white patches that result from melanocyte destruction. The overall pathogenesis of vitiligo remains to be elucidated. Nevertheless, considerable research indicates that adaptive immune activation plays a key role in this process. Specifically, the interferon-gamma (IFN-γ), C-X-C motif chemokine ligands (CXCL9/10), and C-X-C motif chemokine receptor (CXCR3) signaling axis, collectively referred to as IFN-γ-CXCL9/10-CXCR3 or ICC axis, has emerged as a key mediator responsible for the recruitment of autoimmune CXCR3+ CD8+ T cells. These cells serve as executioners of melanocytes by promoting their detachment and apoptosis. Moreover, IFN-γ is generated by activated T cells to create a positive feedback loop, exacerbating the autoimmune response. This review not only delves into the mechanistic insights of the ICC axis but also explores the significant immunological effects of associated cytokines and their receptors. Additionally, the review provides a thorough comparison of existing and emerging treatment options that target the ICC axis for managing vitiligo. This review aims to foster further advancements in basic research within related fields and facilitate a deeper understanding of alternative treatment strategies targeting different elements of the axis.

Keywords: CD8+ T cells; Cytokine axis; Treatment; Vitiligo.

Publication types

  • Review

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Humans
  • Interferon-gamma
  • Receptors, CXCR3
  • Vitiligo* / therapy

Substances

  • Interferon-gamma
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Receptors, CXCR3
  • CXCL9 protein, human
  • CXCL10 protein, human
  • CXCR3 protein, human