| Dissertation |
Thesis (Ph.D.) --NUI, 2010 at Department of Medicine, UCC. |
| Summary |
Background: Dendritic cells (DCs) are a heterogeneous population of potent antigen presenting cells which activate naïve T cell responses. Intestinal DC responses are distinct from systemic responses in that they induce tolerance to antigens which systemically would induce inflammation. How DCs, which are derived from common precursors, can induce such disparate responses is currently under intense investigation. Aim: The aim of the work presented in this thesis was to evaluate the response of DCs isolated from both systemic and gut-associated areas and to assess their response to stimulation both in vitro and in vivo. In addition we aimed to determine the influence of bacteria and the epithelial layer in the induction of tolerance responses in naïve DCs and bone marrow-derived precursor cells. Results: Our investigations revealed differences in the responsiveness of gut-associated DCs and systemic DCs which were underpinned by toll-like receptor (TLR) expression and TLR regulatory proteins. In addition, the differentiation stage of the cell determined the type of response elicited by commensal bacteria, as naïve DCs induce robust Th1 responses to commensal bacteria, while bone marrow precursors induced regulatory responses similar to those observed in Peyer's patch (PP) DCs. Epithelial cells were also found to induce regulatory responses in bone marrow precursors, although the mechanism of this regulation was not similar to that observed in bacteria-conditioned bone marrow-derived cells. Conclusion: Peyer's patch DCs are governed by a distinct pattern of TLR regulation which may have its origins in signals produced by both bacteria and epithelial cells. Unravelling the molecular mechanisms of tolerance responses in gut-associated DCs will aid in promoting resistance to intestinal infection and re-capitulation these mechanisms in precursor cells may aid in the resolution of inflammation. |
| Subject |
Medicine.
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| Collection |
Theses Ph.D.
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Theses Medicine Department
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Theses Alimentary Pharmabiotic Centre
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| Description |
240 p. : ill. ; 30 cm. |
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