# Pathogenesis of Vitiligo: Integrating Immune and Non‐Immune Cell Crosstalk

## TL;DR

This paper reviews how immune and non-immune cells interact in vitiligo, a skin condition, and suggests it may be a systemic disease.

## Contribution

The paper provides a comprehensive review of immune and non-immune cell interactions in vitiligo pathogenesis.

## Key findings

- Cytotoxic CD8+ T cells and IFN-γ are central to vitiligo's pathogenesis.
- Non-lesional skin in vitiligo shows primed pathogenic changes.
- The involvement of multiple immune and non-immune cells suggests a systemic disease model.

## Abstract

Vitiligo is an acquired autoimmune disease characterized by depigmented macules resulting from melanocyte loss. It is a complex multifactorial disorder in which genetic predisposition is combined with environmental factors; however, its detailed etiology remains unclear. Although Janus kinase (JAK) inhibitors have recently emerged as a therapeutic option, the range of available molecularly targeted drugs is limited compared to those for atopic dermatitis or psoriasis, necessitating an urgent elucidation of its pathogenesis. The pathogenesis of vitiligo is centrally mediated by cytotoxic CD8+ T cells (CTLs) specific for melanocyte antigens and their production of interferon‐gamma (IFN‐γ). In recent years, however, the involvement of other immune cells, such as resident memory T cells and regulatory T cells, innate immune cells, and non‐immune cells including keratinocytes and fibroblasts has also garnered attention. Furthermore, pathogenic alterations are also present in clinically normal‐appearing non‐lesional skin, indicating that this tissue is “primed” for disease development. This finding supports a paradigm shift toward viewing vitiligo as a systemic disease rather than a localized skin disorder. Herein, this review summarizes the current knowledge on the factors leading to the onset and progression of non‐segmental vitiligo, while also briefly addressing segmental vitiligo.