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Title: Studies of intestinal inflammation : the roles of IL-23R, gamma-delta T-cells and IL-21i
Author: Shale, Matthew
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2013
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The aetiology of the inflammatory bowel diseases ulcerative colitis and Crohn’s disease remains uncertain. Genetic studies and model systems strongly implicate components of the IL-23/type-17 axis in the pathogenesis of disease, but the cellular and molecular mediators are uncertain. Using an IL-23Rgfp reporter mouse we analysed the cellular expression of IL-23R in homeostasis and disease. Whereas steady state expression in the intestine was dominated by a collection of unconventional lymphoid cells including ;gamma& ;delta& T-cells, we found rapid accumulation of IL-23R+CD4+-/- mice developing increased bacterial colonisation and severe colitis, shown to be driven by increased Th1/IFN-;gamma& responses. These studies provide novel insights into aspects of IL-23 driven cellular and molecular pathways in homeostasis and inflammation in the intestine, with implications for future therapeutic approaches to IBD.
Supervisor: Powrie, Fiona Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Gastroenterology ; Immunology ; colitis ; intestine ; T-cell