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dc.contributor.authorHarris, John E.
dc.contributor.authorHarris, Tajie H.
dc.contributor.authorWeninger, Wolfgang
dc.contributor.authorWherry, E. John
dc.contributor.authorHunter, Christopher A.
dc.contributor.authorTurka, Laurence A.
dc.date2022-08-11T08:08:17.000
dc.date.accessioned2022-08-23T15:49:16Z
dc.date.available2022-08-23T15:49:16Z
dc.date.issued2012-07-01
dc.date.submitted2014-10-03
dc.identifier.citationJ Invest Dermatol. 2012 Jul;132(7):1869-76. doi: 10.1038/jid.2011.463. Epub 2012 Feb 2. <a href="http://dx.doi.org/10.1038/jid.2011.463">Link to article on publisher's site</a>
dc.identifier.issn0022-202X (Linking)
dc.identifier.doi10.1038/jid.2011.463
dc.identifier.pmid22297636
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28393
dc.description.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 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22297636&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343174/
dc.subjectAdoptive Transfer
dc.subjectAnimals
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectDisease Models, Animal
dc.subjectHumans
dc.subjectInterferon-gamma
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectSkin
dc.subjectSkin Pigmentation
dc.subjectVitiligo
dc.subjectgp100 Melanoma Antigen
dc.subjectDermatology
dc.subjectImmune System Diseases
dc.subjectSkin and Connective Tissue Diseases
dc.subjectVeterinary Pathology and Pathobiology
dc.titleA mouse model of vitiligo with focused epidermal depigmentation requires IFN-gamma for autoreactive CD8(+) T-cell accumulation in the skin
dc.typeJournal Article
dc.source.journaltitleThe Journal of investigative dermatology
dc.source.volume132
dc.source.issue7
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/derm_pubs/58
dc.identifier.contextkey6201203
html.description.abstract<p>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.</p>
dc.identifier.submissionpathderm_pubs/58
dc.contributor.departmentDepartment of Medicine, Division of Dermatology
dc.source.pages1869-76


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