University of SaskatchewanHARVEST
  • Login
  • Submit Your Work
  • About
    • About HARVEST
    • Guidelines
    • Browse
      • All of HARVEST
      • Communities & Collections
      • By Issue Date
      • Authors
      • Titles
      • Subjects
      • This Collection
      • By Issue Date
      • Authors
      • Titles
      • Subjects
    • My Account
      • Login
      JavaScript is disabled for your browser. Some features of this site may not work without it.
      View Item 
      • HARVEST
      • Electronic Theses and Dissertations
      • Graduate Theses and Dissertations
      • View Item
      • HARVEST
      • Electronic Theses and Dissertations
      • Graduate Theses and Dissertations
      • View Item

      IL-10-differentiated dendritic cells treatment for Experimental Autoimmune Encephalomyelitis (EAE), a model of human Multiple Sclerosis

      Thumbnail
      View/Open
      Thesis.pdf (1.058Mb)
      Date
      2010-05
      Author
      Xie, Siyuan
      Type
      Thesis
      Degree Level
      Masters
      Metadata
      Show full item record
      Abstract
      Multiple sclerosis is a chronic autoimmune neurological disease characterized by inflammatory cell infiltration and demyelination in the central nervous system (CNS). It is considered to be mediated by Th1 and Th17 immune responses. Experimental autoimmune encephalomyelitis (EAE) is widely used as a mouse model to study MS as it has features and histopathology similar to that of MS. Tolerogenic dendritic cells (DC) are reported to efficiently prevent sensitization for EAE. In this research, we induced tolerogenic DC (DC10) by differentiating them with IL-10. Compared to immature DC, DC10 did not show increased expression of MHC II or the co-stimulatory molecules CD40, CD80 and CD86, and produced low levels of pro-inflammatory cytokines IL-1β, IL-6, and IL-12 but higher levels of IL-10. This is consistent with their possessing a tolerogenic phenotype. We found that three intraperitoneal (i.p.) injections of DC10 successfully inhibited the signs of established, ongoing EAE: DC10 significantly reduced the clinical scores, demyelination and cell infiltration in the spinal cord, as well as the production of IL-4, IL-6, IL-10, IL-17 and IFN-ɣ by spleen and lymph node (LN) lymphocytes. DC10 treatments did not significantly affect inflammatory cytokine mRNA levels in the CNS. We found that there was higher FoxP3 expression in the CNS in response to DC10 treatments relative to PBS-treated animals. We also found that DC10 treatments significantly enhanced IgG1, IgG2a and IgG2b production and total spleen and LN lymphocyte proliferation following challenge with myelin oligodendrocyte glycoprotein (MOG) antigen. As far as we know, this is the first report showing the successful therapeutic treatment with tolerogenic DC10 of established EAE in mice.
      Degree
      Master of Science (M.Sc.)
      Department
      Veterinary Microbiology
      Program
      Veterinary Microbiology
      Supervisor
      Gordon, John
      Committee
      Gerdts, Volker; Tabel, Henry; Misra, Vikram; Singh, Baljit
      Copyright Date
      May 2010
      URI
      http://hdl.handle.net/10388/etd-05192010-172019
      Subject
      multiple sclerosis
      EAE
      tolerance
      dendritic cell
      CNS
      inflammation
      Collections
      • Graduate Theses and Dissertations
      University of Saskatchewan

      University Library

      The University of Saskatchewan's main campus is situated on Treaty 6 Territory and the Homeland of the Métis.

      © University of Saskatchewan
      Contact Us | Disclaimer | Privacy