Studies of intestinal inflammation: the roles of IL-23R, gamma-delta T-cells and IL-21i

Thesis

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-23R^gfp 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.

Authors: Shale, M

• Publication date: 2013
• DOI: 10.5287/ora-kzok7oodr
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: T-cell; colitis; IL-21; intestine; IL-23
• Subjects: Immunology; Gastroenterology