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Title: The role of IL-1beta in intestinal inflammation
Author: Coccia, Margherita
ISNI:       0000 0004 2726 6538
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2011
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Although very high levels of IL 1β are present in the intestines of patients suffering from Inflammatory Bowel Diseases (IBD), little is known about the contribution of IL 1β to intestinal pathology. In the work presented in this thesis, I used several mouse models of chronic intestinal inflammation to address the role of IL 1β in driving innate and adaptive immune pathology in the intestine. My results showed that IL 1β promotes innate immune pathology in Helicobacter hepaticus triggered innate intestinal inflammation, by augmenting the recruitment of granulocytes and the accumulation and activation of a population of IFN γ and IL 17A producing innate lymphoid cells (ILC). To specifically investigate the role of IL 1R signaling on pathogenic T cell responses in the intestine, I used a T cell transfer colitis model. My results demonstrated a key role for IL 1R signals in promoting the accumulation and survival of pathogenic CD4+ T cells in the colon, particularly CD4+ IL 17A+ Th17 cells. Finally, because mutations in the NOD2 gene have been strongly associated with susceptibility to IBD, I investigated the contribution of NOD2 in the H.hepaticusinduced innate immune IBD model. I found that NOD2 expression was significantly increased in the inflamed colon. Furthermore, my preliminary studies suggested that NOD2 played a pro inflammatory role in innate immune colitis, but that NOD2 had little impact on H.hepaticus colonization of the mouse intestine. In summary, my results identify multiple mechanisms through which IL 1β promotes intestinal pathology and suggesting that targeting IL 1β, or innate immune receptors, may represent a useful therapeutic approach in IBD.
Supervisor: Maloy, Kevin Sponsor: Edward Penley Abraham Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Immunology ; Gastroenterology ; Medical Sciences