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Fair, Kathryn L. (2024) Investigating the initiation & progression of ulcerative colitis. PhD thesis, University of Nottingham.

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Abstract

Inflammatory bowel disease (IBD) is a significant and ever-growing problem in developed countries, with recent increased prevalence throughout Eastern countries. It is an idiopathic, progressive disease characterised by chronic GI inflammation, the aetiology of which remains largely unknown. Inflammatory phenotypes differ between healthy & IBD patients with dysregulated immune responses suspected to play a critical role in disease pathogenesis.

Toll-like receptors have been implicated in the pathogenesis of IBD, in particular TLR4. TLR4 recognises lipopolysaccharides (LPS) present on the surface of Gram-negative bacteria which appear to be in greater abundance in IBD patients. By further understanding the implications of this signalling pathway, therapeutic approaches with enhanced efficacy can be employed.

A primary 3D model generated from the colonic crypts was utilized to explore critical differences in the response of healthy tissue and that derived from ulcerative colitis patients. Once multiple patient lines were generated, a combination of analytical techniques were employed to investigate any inflammatory & fibrotic alterations that occur upon exposure to inflammatory agents, inclusive of bacterial antigens, and whether these changes are reversed following treatment with existing and novel anti-inflammatory agents.

In conclusion, a clear and substantial differential response was demonstrated between healthy & UC-derived colonic organoids, displaying a significant disease phenotype. The TLR4 inflammatory pathway, identified as being greatly responsible for many of these differences, triggers an exaggerated response to the presence of bacterial PAMPs in UC.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Hannan, Nick Monaghan, Tanya
Keywords:	Inflammatory bowel disease; Inflammatory pathways; Toll-like receptors
Subjects:	W Medicine and related subjects (NLM Classification) > WI Digestive system
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	78615
Depositing User:	Fair, Kathryn
Date Deposited:	11 Dec 2024 04:40
Last Modified:	11 Dec 2024 04:40
URI:	https://eprints.nottingham.ac.uk/id/eprint/78615

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