T CELLS IN THE PATHOGENESIS OF SPONTANEOUS AUTOIMMUNE PERIPHERAL POLYNEUROPATHY Public Deposited

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  • March 21, 2019
Creator
  • Smith, Collin-Jamal
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
Abstract
  • The immune system defends the body from pathogens, and its function is essential for life. Adaptive immunity protects the host through specific targeting and elimination of pathogens and toxins. However, due to the stochastic nature of adaptive immune cell antigen specificity, cells that attack the host are inadvertently generated. Autoimmunity, or immune attack against the host, causes severe morbidity and mortality in the population. Furthermore, treatments of autoimmune diseases often have limited efficacy and serious side-effects. To develop better treatments for autoimmunity, the underlying pathogenesis must be understood. For my thesis, I studied a mouse model of chronic inflammatory demyelinating polyneuropathy (CIDP) to understand the mechanisms behind disease. CIDP is a debilitating condition caused by autoimmune demyelination of peripheral nerves. In my studies, I researched the role of T lymphocytes, the immunosuppressive cytokine interleukin 10 (IL-10), and other immune cells and markers in NOD.AireGW/+ mice that develop spontaneous autoimmune peripheral polyneuropathy (SAPP) that resembles CIDP. I demonstrated that T cells are required for SAPP, and that IL-10 paradoxically exacerbates SAPP. I delineated a novel mechanism in which IL-10-induced STAT3 increases S1pr1 expression and CD4+ T cell migration to accelerate T cell-mediated destruction of peripheral nerves. My results suggest the increased IL-10 expression observed in CIDP patients may be a marker of disease activity and progression rather than immunosuppression.
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Rights statement
  • In Copyright
Advisor
  • Tisch, Roland
  • Deshmukh, Mohanish
  • Miao, Edward
  • Su, Maureen
  • Wan, Yisong
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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