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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 depigmentat...

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Autores principales: Harris, John E., Harris, Tajie H., Weninger, Wolfgang, Wherry, E. John, Hunter, Christopher A., Turka, Laurence A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343174/
https://www.ncbi.nlm.nih.gov/pubmed/22297636
http://dx.doi.org/10.1038/jid.2011.463
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author Harris, John E.
Harris, Tajie H.
Weninger, Wolfgang
Wherry, E. John
Hunter, Christopher A.
Turka, Laurence A.
author_facet Harris, John E.
Harris, Tajie H.
Weninger, Wolfgang
Wherry, E. John
Hunter, Christopher A.
Turka, Laurence A.
author_sort Harris, John E.
collection PubMed
description 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 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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spelling pubmed-33431742013-01-01 A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8(+) T cell accumulation in the skin Harris, John E. Harris, Tajie H. Weninger, Wolfgang Wherry, E. John Hunter, Christopher A. Turka, Laurence A. J Invest Dermatol Article 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 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. 2012-02-02 2012-07 /pmc/articles/PMC3343174/ /pubmed/22297636 http://dx.doi.org/10.1038/jid.2011.463 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Harris, John E.
Harris, Tajie H.
Weninger, Wolfgang
Wherry, E. John
Hunter, Christopher A.
Turka, Laurence A.
A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8(+) T cell accumulation in the skin
title A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8(+) T cell accumulation in the skin
title_full A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8(+) T cell accumulation in the skin
title_fullStr A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8(+) T cell accumulation in the skin
title_full_unstemmed A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8(+) T cell accumulation in the skin
title_short A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8(+) T cell accumulation in the skin
title_sort mouse model of vitiligo with focused epidermal depigmentation requires ifn-γ for autoreactive cd8(+) t cell accumulation in the skin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343174/
https://www.ncbi.nlm.nih.gov/pubmed/22297636
http://dx.doi.org/10.1038/jid.2011.463
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