A Mouse Model of Vitiligo with Focused Epidermal Depigmentation Requires IFN-γ for Autoreactive \(CD8^+\) T Cell Accumulation in the Skin
Harris, Tajie H.
Wherry, E. John
Hunter, Christopher A.
Harris, John E.
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CitationHarris, John E., Tajie H. Harris, Wolfgang Weninger, E. John Wherry, Christopher A. Hunter, and Laurence A. Turka. 2012. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive \(CD8^+\) T cell accumulation in the skin. The Journal of Investigative Dermatology 132(7): 1869-1876.
AbstractVitiligo 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 interferon-gamma (IFN-γ) is increased in the lesional skin of patients, however it is currently unknown what role IFN-γ plays 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.
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