Queen's University - Utility Bar

QSpace at Queen's University >
Theses, Dissertations & Graduate Projects >
Queen's Theses & Dissertations >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1974/6666

This item is restricted and will be released 2016-08-22.
Title: IMPACT OF RNA VIRUSES ON THE REGULATION OF IL-23 IN MOUSE AND HUMAN MODELS OF INFECTION.
Authors: CHE MAT, NOR FAZILA

Files in This Item:

File Description SizeFormat
Che Mat_Nor Fazila_201108_PhD.pdf2.91 MBAdobe PDFView/Open
Keywords: Virus
Interleukin-23 (IL-23)
Issue Date: 24-Aug-2011
Series/Report no.: Canadian theses
Abstract: Interluekin-23 (IL-23) is a pro-inflammatory cytokine critical to the regulation of innate and adaptive immune responses. The main role for this cytokine is in the proliferation and differentiation of the IL-17 producing CD4 T helper cell, Th17. Virus infection deregulates IL-23 expression and function, but little is known about the mechanism behind this phenomena. Here, I demonstrate a reduction of Toll like receptor (TLR) ligand-induced IL-23 expression in lymphocytic choriomeningitis virus (LCMV)-infected bone marrow-derived dendritic cells (BMDCs), indicating that a function of these cells is disrupted during virus infection. I propose a mechanism of TLR ligand-induced IL-23 expression inhibition upon LCMV infection via the deactivation of p38, AP-1, and NF-κB. Further analysis revealed a direct relationship between LCMV infection with the IL-10 and SOCS3 expression. To understand IL-23 function, I characterized IL-23-induced JAK/STAT signalling pathway and IL-23 receptor expression on human CD4 T cells. My results demonstrate that IL-23 induces activation of p-JAK2, p-Tyk2, p-STAT1, p-STAT3, and p-STAT4 in CD4 T cells. For the first time I show that IL-23 alone induces the expression of its own receptor components, IL-12Rβ1 and IL-23Rα, in CD4 T cells. Blocking JAK2, STAT1, and STAT3 activation with specific inhibitors detrimentally effected expression of IL-23 receptor demonstrating that activation of JAK/STAT signalling is important for IL-23 receptor expression. I also addressed the effect of viral infection on IL-23 function and receptor expression in CD4 T cells using cells isolated from HIV positive individuals. These studies were based on earlier reports that the expression of IL-23 and the IL-23 receptor are impaired during HIV infection. I demonstrate that the phosphorylation of JAK2, STAT1, and STAT3 induced by IL-23, as well as IL-23 receptor expression are deregulated in CD4 T cells isolated from HIV positive individuals. This study has furthered the understanding of how the expression and function of IL-23 is regulated during viral infections.
Description: Thesis (Ph.D, Microbiology & Immunology) -- Queen's University, 2011-08-24 07:52:24.898
URI: http://hdl.handle.net/1974/6666
Appears in Collections:Queen's Theses & Dissertations
Microbiology & Immunology Graduate Theses

Items in QSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

  DSpace Software Copyright © 2002-2008  The DSpace Foundation - TOP