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Title: The expression and regulation of thrombospondin-1 in the murine immune system
Author: Self-Fordham, Jezrom Bokcaerin
ISNI:       0000 0004 2734 0013
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2011
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Thrombospondin-1 (TSP-l) is a multi functional protein, which is secreted into the extracellular matrix during inflammation where it modulates numerous components of the immune infiltrate. TSP-l can inhibit T cell proliferation and induce apoptosis through CD47 ligation, as well as contributing to an immunosuppressive, anti-inflammatory environment via its ability to activate latent Transforming Growth Factor-beta (TGF-B). TSP-l is constitutively expressed by the retinal pigment epithelium of the eye where it plays a role in conferring immunological privilege. Discrepancy exists in the published data describing the type of immune cells that produce TSP-l, both within and between the murine and other systems. The data presented in this thesis sets out to describe the immune cells that produce TSP-I and the signals that control its expression. I studied the cells of the murine immune system and ascribe TSP-l production to monocyte-derived cells, predominantly macrophages, and show that innate and inflammatory signals are strong inducers of TSP-l production in these cells. While the notion of macro phages as TSP-1 producers is in accordance with the majority of the literature I go on to show that Th cells of various lineages and activation states do not produce significant amounts of TSP-1- an observation that is in opposition to certain published data. However, I also show that in two in vivo models of inflammation the production of TSP-l segregates to myeloid-derived cells and not to T cells. The observation that Th cytokines differentially regulate this expression may go some way to reconciling our data with others. I show that cytokines from Thl and Th2, but not Th 17 cells ablate TSP-l expression in activated macrophages. In summary I show that the local production of TSP- t is controlled by environmental cues that include innate and inflammatory signals as well as those produced during adaptive immunity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available