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    The Role of ITK in the Development of Gamma Delta NKT Cells: A Dissertation

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    Authors
    Yin, Catherine C
    Faculty Advisor
    Leslie J. Berg, Ph.D.
    Academic Program
    Immunology and Microbiology
    UMass Chan Affiliations
    Pathology
    Document Type
    Doctoral Dissertation
    Publication Date
    2012-08-08
    Keywords
    Protein-Tyrosine Kinases
    Natural Killer T-Cells
    Amino Acids, Peptides, and Proteins
    Cells
    Enzymes and Coenzymes
    Hemic and Immune Systems
    Immunology and Infectious Disease
    Pharmaceutical Preparations
    Therapeutics
    Tissues
    
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    Abstract
    The immune system is a complex network of interacting cells and tissues that is designed to protect the body from pathogens and other foreign substances. T cells are a major component of the immune system and consist of two distinct lineages distinguished by the expression of αβ or γδ T cell receptors (TCR). The Tec family kinase, Itk is an important mediator of signaling downstream of the TCR. Past studies on Itk has focused on how Itk regulates development, activation and differentiation of conventional αβ T cells and more recently how Itk regulates the development of innate-like αβ T cells. However, very little is known about the influence of Itk on γδ T cells. My studies show a previously unknown role for Itk in the development and function of γδ T cells. We report in the absence of Itk, γδ T cells were responsible for the spontaneously elevated levels of serum IgE and Itk-/- mice γδ T cells produced high levels of TH2 cytokines. Furthermore, there was an increase in γδ T cells specifically in the Vγ1.1+Vδ6.3+ (V6) subset that represents the dominant population of γδ NKT cells in Itk-/- mice. In addition, the V6 subset had increased expression of PLZF, a transcription factor normally required for αβ iNKT cell development. We further show that V6 cells develop and mature similar to αβ iNKT cells. Similar to defects previously seen in the terminal differentiation of Itk-/- αβ iNKT cell, V6 cells also had impaired maturation in the thymus in the absence of Itk. This data demonstrates a previously unknown role of Itk for the terminal maturation of V6 cells that has been shown to be the cell population that led to spontaneous dermatitis in mice. Given that drug companies have targeted Itk as a potential allergy drug due to Itk’s role in TH2 development and function, our data suggests that further studies on Itk are warranted.
    DOI
    10.13028/mjv4-tw64
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/31986
    Rights
    Copyright is held by the author, with all rights reserved.
    ae974a485f413a2113503eed53cd6c53
    10.13028/mjv4-tw64
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    Morningside Graduate School of Biomedical Sciences Dissertations and Theses

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