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The immunology of vitiligo

Nature Reviews Immunology (2026)Cite this article

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Abstract

Vitiligo is an autoimmune disease of melanocyte destruction, which manifests as progressive, patchy loss of pigmentation in the skin. As one of most common autoimmune diseases, vitiligo inflicts a significant psychosocial burden. Research over the past two decades has revealed the underlying immune mechanisms of vitiligo, with key studies combining detailed analyses of patient tissue samples with mechanistic experiments in mouse models. Vitiligo has emerged as a prototypical CD8+ T cell-mediated autoimmune disease, with cooperation between innate immune cells, dendritic cells, T cells, keratinocytes and fibroblasts driving autoimmune pathology against the uniquely susceptible melanocyte target. The study of vitiligo has also revealed aspects of CD8+ T cell memory and resident memory against self-antigens. This work has drawn from, and contributed to, the study of melanoma immunology. Whereas drugs used for other autoimmune conditions have been largely ineffective in treating vitiligo, a growing base of knowledge recently led to the first successful FDA-approved immune-modulating drugs for vitiligo. This review focuses on the immunology of vitiligo: the mechanisms that drive melanocyte destruction, the biology of aberrant T cell responses against melanocytes and therapeutic means for counteracting this autoimmune condition.

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Fig. 1: Vitiligo susceptibility factors and innate immune activation.
Fig. 2: Mouse models of vitiligo.
Fig. 3: Essential roles for IFNγ, keratinocytes, fibroblasts and CD8+ T cells in vitiligo.
Fig. 4: The role of memory CD8+ T cells in vitiligo.

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Authors and Affiliations

  1. The Dartmouth Cancer Center and the Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

    Mary Jo Turk & Yina H. Huang

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Glossary

Altered peptide ligands

Peptides differing in one or more amino acids from an original peptide, which bind to MHC proteins and promote TCR signalling.

Autoimmune regulator

(AIRE). A transcription factor that promotes the expression of tissue-specific antigens in the thymus, enabling the elimination of self-reactive T cells.

Central tolerance

The process by which self-reactive T cells are eliminated during their development in the thymus.

Cross-presenting

A term used for DCs that present phagocytosed antigens on cell-surface MHC class I molecules.

Dermatome

An area of skin innervated by a single spinal nerve root.

Desmoglein

A cadherin protein involved in cell–cell adhesion and tissue integrity.

K14-SCF

A transgene in which SCF expression is driven by the keratin-14 promoter, allowing for epidermal homing of melanocytes.

Koebner phenomenon

The appearance of new skin lesions on previously unaffected skin following trauma or injury.

Nevus

A benign skin growth caused by proliferation of melanocytes.

Phenolic compounds

A group of chemical substances found in plants and some industrial products that contain one or more hydroxyl groups attached to an aromatic ring.

Psoralen

A naturally occurring chemical compound found in some plants that makes skin more sensitive to UV light.

Smyth line chicken vitiligo

A naturally occurring autoimmune depigmentation condition seen in a highly inbred strain of chickens.

Tyrosinase

A key enzyme involved in the production of melanin.

Unfolded protein response

A cellular stress response triggered when misfolded or unfolded proteins accumulate in the endoplasmic reticulum.

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Turk, M.J., Huang, Y.H. The immunology of vitiligo. Nat Rev Immunol (2026). https://doi.org/10.1038/s41577-025-01249-z

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