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Role of Type I Interferon Signalling in Regulating Cell Survival, Proliferation, and Cytokine Production in Antigen-Presenting Cells

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Title: Role of Type I Interferon Signalling in Regulating Cell Survival, Proliferation, and Cytokine Production in Antigen-Presenting Cells
Author: Rasiuk, Alexandra S.
Department: Department of Pathobiology
Program: Pathobiology
Advisor: Bridle, Byram W.
Abstract: During viral infections, cells produce cytokines called type I interferons (IFNs), which are detected by the IFNa/b receptor (IFNAR). To survive in hosts, viruses have strategies to downregulate IFN production, IFNAR expression, and/or downstream signalling components. IFNAR-mediated regulation of IL-1a, IL-6, IL-12, and TNFa was studied in antigen-presenting cells (APCs); specifically, inflammatory dendritic cells (DCs), CD8+ and CD8- classical DCs, plasmacytoid DCs, and macrophages. We hypothesized that downregulation of IFNAR signalling during ligation of Toll-like receptors (TLRs) would result in cytokine dysregulation. Murine APCs were stimulated with lipopolysaccharide or imiquimod to ligate TLR4 and 7, respectively, with or without blocking IFNAR signalling. Cytokines, cell proliferation, and viability were assessed for three days post-stimulation. Blocking the IFNAR caused cytokine upregulation during TLR4 stimulation and downregulation during TLR7 stimulation, suggesting that ligation might particpate in regulating cytokines in IFNAR-associated pathologies. This also provides a cell-based model for the discovery of molecular mechanisms.
URI: http://hdl.handle.net/10214/9196
Date: 2015-09
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