The role of IL-18 in intestinal immune regulation

Thesis

Elevated levels of the cytokine interleukin-18 (IL-18) are found in many chronic inflammatory disorders, including inflammatory bowel disease (IBD). However, the role of IL-18 in mucosal immunity and inflammation is not well understood. At mucosal and environmental interfaces, Th17 cells have been shown to contribute to protection from pathogenic infection. In contrast, regulatory T (Treg) cells maintain intestinal homeostasis by preventing aberrant inflammatory responses to the resident microbiota. We demonstrate that under homeostatic conditions, colonic Th17 cells highly express IL-18 receptor (IL-18R1) and that intestinal epithelial cell production of IL-18 acts directly on CD4⁺ T cells to limit colonic Th17 differentiation. Furthermore, whilst IL-18R1-signalling is dispensable for induction of colitis, we observed a critical role for IL-18R1-signalling in Foxp3⁺ Treg mediated control of colitis. Together, these studies demonstrate that the intestinal epithelium regulates colonic CD4⁺ T cell responses through production of the cytokine IL-18.

Authors: Harrison, O; Oliver J Harrison

• Publication date: 2013
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: Oxford University, UK
• Language: English
• Keywords: Intestine; IL-18; Th17; Immunity; Foxp3
• Subjects: Gastroenterology; Immunology