Rigby, Rachael Jane;
(2004)
Intestinal dendritic cells: Characterisation of the colonic dendritic cell population and identification of potential precursors.
Doctoral thesis (Ph.D), University College London.
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Abstract
Dendritic cells (DC) are sentinels of the immune response and have the ability to influence the type of immune response they initiate. The role of DC in gut mucosa is to regulate tolerogenic as well as stimulatory responses upon exposure to antigenic material, but at present colonic DC have been poorly characterised. We hypothesized that the diverse functions of intestinal DC could be attributed to antigenic exposure, as different stimuli, including microbes and their products, have distinct effects on DC, or to the recruitment of pre-determined precursor populations. In this thesis the development of methods for identification and characterisation of murine colonic DC from normal animals, and analysis of phenotypic and functional properties of these DC are described. Colonic DC, extracted using enzymatic digestion, stimulated allogeneic T-cells and expressed co-stimulatory molecules, properties that were enhanced following overnight culture. Murine colonic tissue was devoid of CD8α+ DC, although this subset was detected in Peyer's patches. To determine colonic DC responses to bacterial antigens, we assessed intracellular IL-12 and IL-10 production, both before, and following stimulation with LPS or Bifidobacteria longum. Cell wall components from different bacteria stimulated different cytokine production, and therefore may have the potential to direct differentially developing acquired immune responses in gut. α4β7 integrin mediates lymphocyte and mast cell homing to the intestine through binding MADCAM-1 expressed on gut endothelial cells. These studies identify five populations of HLA-DR+ Lineage-/dim DC in human blood, based on their differential expression of β7 and CDllc integrins. Discrete β7+ DC subsets co-expressed CLA and/or CDlc, involved in homing to skin. β7-expressing DC may have a higher propensity to home to intestine and together with other external influences are potentially precursors of specialised intestinal DC. Both exposure to bacterial stimuli, and recruitment of pre determined precursors may contribute to the specialised properties of intestinal DC.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Intestinal dendritic cells: Characterisation of the colonic dendritic cell population and identification of potential precursors. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10101800 |
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