The role of IL-18 in intestinal immune regulation
<p>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 ha...
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| Format: | Thesis |
| Language: | English |
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2013
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| _version_ | 1826310517477605376 |
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| author | Harrison, OJ |
| author2 | Maloy, K |
| author_facet | Maloy, K Harrison, OJ |
| author_sort | Harrison, OJ |
| collection | OXFORD |
| description | <p>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<sup>+</sup> 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<sup>+</sup> Treg mediated control of colitis. Together, these studies demonstrate that the intestinal epithelium regulates colonic CD4<sup>+</sup> T cell responses through production of the cytokine IL-18.</p> |
| first_indexed | 2024-03-07T07:53:10Z |
| format | Thesis |
| id | oxford-uuid:86cd89b1-8652-48d9-a37a-d34ec2bba8b7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:53:10Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:86cd89b1-8652-48d9-a37a-d34ec2bba8b72023-08-01T09:00:41ZThe role of IL-18 in intestinal immune regulationThesishttp://purl.org/coar/resource_type/c_db06uuid:86cd89b1-8652-48d9-a37a-d34ec2bba8b7ImmunologyGastroenterologyEnglishOxford University Research Archive - Valet2013Harrison, OJMaloy, KKlenerman, P<p>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<sup>+</sup> 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<sup>+</sup> Treg mediated control of colitis. Together, these studies demonstrate that the intestinal epithelium regulates colonic CD4<sup>+</sup> T cell responses through production of the cytokine IL-18.</p> |
| spellingShingle | Immunology Gastroenterology Harrison, OJ The role of IL-18 in intestinal immune regulation |
| title | The role of IL-18 in intestinal immune regulation |
| title_full | The role of IL-18 in intestinal immune regulation |
| title_fullStr | The role of IL-18 in intestinal immune regulation |
| title_full_unstemmed | The role of IL-18 in intestinal immune regulation |
| title_short | The role of IL-18 in intestinal immune regulation |
| title_sort | role of il 18 in intestinal immune regulation |
| topic | Immunology Gastroenterology |
| work_keys_str_mv | AT harrisonoj theroleofil18inintestinalimmuneregulation AT harrisonoj roleofil18inintestinalimmuneregulation |