A mouse model of vitiligo with focused epidermal depigmentation requires IFN-gamma for autoreactive CD8(+) T-cell accumulation in the skin
Department of Medicine, Division of Dermatology
Medical Subject Headings
Adoptive Transfer; Animals; CD8-Positive T-Lymphocytes; Disease Models, Animal; Humans; Interferon-gamma; Mice; Mice, Inbred C57BL; Skin; Skin Pigmentation; Vitiligo; gp100 Melanoma Antigen
Dermatology | Immune System Diseases | Skin and Connective Tissue Diseases | Veterinary Pathology and Pathobiology
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-gamma is increased in the lesional skin of patients, however, it is currently unknown what role IFN-gamma 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-gamma production. Neutralization of IFN-gamma with antibody prevents CD8(+) T-cell accumulation and depigmentation, suggesting a therapeutic potential for this approach.
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Citation: J Invest Dermatol. 2012 Jul;132(7):1869-76. doi: 10.1038/jid.2011.463. Epub 2012 Feb 2. Link to article on publisher's site
Harris, John E.; Harris, Tajie H.; Weninger, Wolfgang; Wherry, E. John; Hunter, Christopher A.; and Turka, Laurence A., "A mouse model of vitiligo with focused epidermal depigmentation requires IFN-gamma for autoreactive CD8(+) T-cell accumulation in the skin" (2012). Dermatology Publications and Presentations. 58.