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    Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo

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    Authors
    Richmond, Jillian M.
    Strassner, James P.
    Zapata, Lucio Jr.
    Garg, Madhuri
    Riding, Rebecca L.
    Refat, Maggi A.
    Fan, Xueli
    Azzolino, Vincent
    Tovar-Garza, Andrea
    Tsurushita, Naoya
    Pandya, Amit G.
    Tso, J Yun
    Harris, John E.
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    UMass Chan Affiliations
    Graduate School of Biomedical Sciences
    Department of Dermatology
    Document Type
    Journal Article
    Publication Date
    2018-07-18
    Keywords
    UMCCTS funding
    vitiligo
    autoimmune diseases
    interleukin-15
    CD122
    Dermatology
    Immune System Diseases
    Immunity
    Immunoprophylaxis and Therapy
    Skin and Connective Tissue Diseases
    Translational Medical Research
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    Link to Full Text
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495055/
    Abstract
    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.
    Source

    Sci Transl Med. 2018 Jul 18;10(450). pii: eaam7710. doi: 10.1126/scitranslmed.aam7710. Link to article on publisher's site

    DOI
    10.1126/scitranslmed.aam7710
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/50379
    PubMed ID
    30021889
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1126/scitranslmed.aam7710
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    UMass Center for Clinical and Translational Science Supported Publications

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