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Title: The role of IL-1beta in intestinal inflammation
Author: Coccia, Margherita
Awarding Body: Oxford University
Current Institution: University of Oxford
Date of Award: 2011
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Although very high levels of IL-1B are present in the intestines of patients suffering from Inflammatory Bowel Diseases (IBD) little is known about the contribution of IL- 1B 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-lB in driving innate and adaptive immune pathology in the intestine. My results showed that IL- 1B 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-y- 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, 1 investigated the contribution of NOD2 in the H.hepaticus- induced 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-lB promotes intestinal pathology and suggesting that targeting IL-lB, or innate immune receptors, may represent a useful therapeutic approach in IBD.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available