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Identifier 000395568
Title The role of endogenous Osteopontin expression in the development and function of Foxp3+ regulatory T cells
Alternative Title Ο ρόλος της ενδογενούς έκφρασης της Οστεοποντίνης στην ανάπτυξη και την λειτουργία των Foxp3+ T ρυθμιστικών λεμφοκυττάρων
Author Σκόρδος, Ιωάννης
Thesis advisor Πανουτσακοπούλου, Β.
Πασχαλίδης, Ν.
Select a value Ηλιόπουλος, Α.
Τσατσάνης, Χ.
Abstract Osteopontin (Opn) is a glycophosphoprotein that is normally expressed by a wide variety of cells types, including activated T cells. Opn is involved in many physiological processes such as chemotaxis, cell adhesion and apoptosis. Many studies have described a crucial role of Opn in immune mediated diseases and tumor metastasis. Previous work from our group has demonstrated that Opn has anti-allergic effects during secondary antigenic challenge in a mouse model of allergic airway inflammation (Xanthou et al., 2007). Further studies in our laboratory suggested that these protective effects were partially mediated by Foxp3+ Tregs. Interestingly, Opn gene (Spp1) is one of the few significantly upregulated genes in stimulated Foxp3+ Treg cells (Do et al., 2015; Marson et al., 2007); however its role in the generation and function of these cells remains elusive. The aim of our project was to investigate the effects of endogenous Opn on development and function of Foxp3+ Treg cells. Our data showed that Opn expression is required for optimal Foxp3 induction in transforming growth factor-beta (TGF-β)-generated Tregs in vitro. We have also observed diminished Foxp3 induction in Opn knockout T cells in an in vivo model of homeostatic expansion of naïve T cells in Rag-/- mice. Furthermore, the effects of genetic deletion of Opn in the function of induced-Treg cells in vitro were investigated and results indicated that Opn is required for their optimal suppressive function. Finally, adoptive transfer experiments of iTreg cells, as a means of protection from the development of allergic airway inflammation, showed that endogenous Opn expression is indispensable for the optimal in vivo suppressive capacity of iTreg cells.
Language English
Subject Ρυθμιστικά Τ λεμφοκύτταρα
Issue date 2015-07-17
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
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