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    Understanding regulatory factors in the skin during vitiligo

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    Authors
    Essien, Kingsley I.
    Faculty Advisor
    John E. Harris
    Academic Program
    Interdisciplinary Graduate Program
    UMass Chan Affiliations
    Dermatology
    Document Type
    Doctoral Dissertation
    Publication Date
    2018-12-08
    Keywords
    Vitiligo
    Regulatory T Cells
    Tregs
    Langerhans cells
    Immune System Diseases
    Immunopathology
    Skin and Connective Tissue Diseases
    
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    Abstract
    Vitiligo is an autoimmune disease of the skin characterized by epidermal depigmentation that results from CD8+ T cell-mediated destruction of pigment producing melanocytes. Vitiligo affects up to 1% of the population and current treatments are moderately effective at facilitating repigmentation by suppressing cutaneous autoimmune inflammation to promote melanocyte regeneration. In order to cause disease, CD8+ T cells must overwhelm the mechanisms of peripheral tolerance in the skin and if we understand the suppressive mechanisms that are compromised during vitiligo, we can potentially use this information to improve existing treatments or engineer novel interventions. Therefore, my goal is to characterize the regulatory factors in the skin that suppress depigmentation during vitiligo. Our lab has developed a mouse model of vitiligo that accurately reflects human disease and I used this model to demonstrate that regulatory T cells suppress CD8+ T cell-mediated depigmentation and interact with CD8+ T cells in the skin during vitiligo. In this model of disease, I investigated the molecules involved in regulatory T cell function and observed that the chemokine receptors CCR5 and CCR6 play different roles in regulatory T cell suppression. While CCR6 facilitates regulatory T cell migration to the skin, CCR5 is dispensable for migration but required for optimal regulatory T cell function. Additionally, I used our mouse model to demonstrate that Langerhans cells suppress the incidence of disease during vitiligo. Taken together the results from these studies provide novel insights into the mechanisms of suppression during vitiligo.
    DOI
    10.13028/x0vt-6m83
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/31233
    Rights
    Copyright is held by the author, with all rights reserved.
    ae974a485f413a2113503eed53cd6c53
    10.13028/x0vt-6m83
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    Morningside Graduate School of Biomedical Sciences Dissertations and Theses

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