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dc.contributor.authorRichmond, Jillian M
dc.contributor.authorStrassner, James P.
dc.contributor.authorZapata, Lucio Jr.
dc.contributor.authorGarg, Madhuri
dc.contributor.authorRiding, Rebecca L.
dc.contributor.authorRefat, Maggi A.
dc.contributor.authorFan, Xueli
dc.contributor.authorAzzolino, Vincent
dc.contributor.authorTovar-Garza, Andrea
dc.contributor.authorTsurushita, Naoya
dc.contributor.authorPandya, Amit G.
dc.contributor.authorTso, J Yun
dc.contributor.authorHarris, John E.
dc.date2022-08-11T08:11:02.000
dc.date.accessioned2022-08-23T17:29:42Z
dc.date.available2022-08-23T17:29:42Z
dc.date.issued2018-07-18
dc.date.submitted2019-10-11
dc.identifier.citation<p>Sci Transl Med. 2018 Jul 18;10(450). pii: eaam7710. doi: 10.1126/scitranslmed.aam7710. <a href="https://doi.org/10.1126/scitranslmed.aam7710">Link to article on publisher's site</a></p>
dc.identifier.issn1946-6234 (Linking)
dc.identifier.doi10.1126/scitranslmed.aam7710
dc.identifier.pmid30021889
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50379
dc.description.abstractVitiligo is an autoimmune disease of the skin mediated by CD8(+) T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (TRM) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and mucosal-tropic viruses. Interleukin-15 (IL-15)-deficient mice reportedly have impaired TRM formation, and IL-15 promotes TRM function ex vivo. We found that both human and mouse TRM express the CD122 subunit of the IL-15 receptor and that keratinocytes up-regulate CD215, the subunit required to display the cytokine on their surface to promote activation of T cells. Targeting IL-15 signaling with an anti-CD122 antibody reverses disease in mice with established vitiligo. Short-term treatment with anti-CD122 inhibits TRM production of interferon-gamma (IFNgamma), and long-term treatment depletes TRM from skin lesions. Short-term treatment with anti-CD122 can provide durable repigmentation when administered either systemically or locally in the skin. On the basis of these data, we propose that targeting CD122 may be a highly effective and even durable treatment strategy for vitiligo and other tissue-specific autoimmune diseases involving TRM.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30021889&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495055/
dc.subjectUMCCTS funding
dc.subjectvitiligo
dc.subjectautoimmune diseases
dc.subjectinterleukin-15
dc.subjectCD122
dc.subjectDermatology
dc.subjectImmune System Diseases
dc.subjectImmunity
dc.subjectImmunoprophylaxis and Therapy
dc.subjectSkin and Connective Tissue Diseases
dc.subjectTranslational Medical Research
dc.titleAntibody blockade of IL-15 signaling has the potential to durably reverse vitiligo
dc.typeJournal Article
dc.source.journaltitleScience translational medicine
dc.source.volume10
dc.source.issue450
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/umccts_pubs/206
dc.identifier.contextkey15534550
html.description.abstract<p>Vitiligo is an autoimmune disease of the skin mediated by CD8(+) T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (TRM) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and mucosal-tropic viruses. Interleukin-15 (IL-15)-deficient mice reportedly have impaired TRM formation, and IL-15 promotes TRM function ex vivo. We found that both human and mouse TRM express the CD122 subunit of the IL-15 receptor and that keratinocytes up-regulate CD215, the subunit required to display the cytokine on their surface to promote activation of T cells. Targeting IL-15 signaling with an anti-CD122 antibody reverses disease in mice with established vitiligo. Short-term treatment with anti-CD122 inhibits TRM production of interferon-gamma (IFNgamma), and long-term treatment depletes TRM from skin lesions. Short-term treatment with anti-CD122 can provide durable repigmentation when administered either systemically or locally in the skin. On the basis of these data, we propose that targeting CD122 may be a highly effective and even durable treatment strategy for vitiligo and other tissue-specific autoimmune diseases involving TRM.</p>
dc.identifier.submissionpathumccts_pubs/206
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentDepartment of Dermatology
dc.source.pageseaam7710


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