A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8⁺ T-cell accumulation in the skin.
Vitiligo is an autoimmune disease of the skin causing disfiguring patchy depigmentation of the epidermis and, less commonly, hair. Therapeutic options for vitiligo are limited, reflecting in part limited knowledge of disease pathogenesis. Existing mouse models of vitiligo consist of hair depigmentation but lack prominent epidermal involvement, which is the hallmark of human disease. They are thus unable to provide a platform to fully investigate disease mechanisms and treatment. CD8(+) T cells have been implicated in the pathogenesis of vitiligo, and expression of IFN-γ is increased in the lesional skin of patients, however, it is currently unknown what role IFN-γ has in disease. Here, we have developed an adoptive transfer mouse model of vitiligo using melanocyte-specific CD8(+) T cells, which recapitulates the human condition by inducing epidermal depigmentation while sparing the hair. Like active lesions in human vitiligo, histology of depigmenting skin reveals a patchy mononuclear infiltrate and single-cell infiltration of the epidermis. Depigmentation is accompanied by accumulation of autoreactive CD8(+) T cells in the skin, quantifiable loss of tyrosinase transcript, and local IFN-γ production. Neutralization of IFN-γ with antibody prevents CD8(+) T-cell accumulation and depigmentation, suggesting a therapeutic potential for this approach.
Division of Dermatology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA. John.Harris@umassmed.edu
John E
JE
Harris
Tajie H
TH
Harris
Wolfgang
W
Weninger
E John
EJ
Wherry
Christopher A
CA
Hunter
Laurence A
LA
Turka
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000276:immunology*; D012880:Skin Pigmentation; D014820:Vitiligo / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D058951:gp100 Melanoma Antigen / Q000032:analysis
C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma