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A genetic regulatory model of interleukin-17-mediated gut inflammation and immunity.

Nicholas Schuh

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Canadian Institutes of Health Research (CIHR)
Intestinal health is maintained by complicated interactions between the cells that make up the intestines, cells of the immune system, and normal bacteria that live in the intestines. When these factors are disturbed, it can lead to conditions like systemic infection with gut bacteria, inflammatory bowel disease, and colorectal cancer. Recently, scientists have discovered that the human immune system makes a molecule called interleukin-17 (IL-17) that regulates inflammation in the gut and other tissues. In humans, production of IL-17 by cells making up the intestines is very important in the development of intestinal disease, but research studies are confounded by other IL-17's from immune cells. Animals like flies and worms, which are traditionally used to study biology from a whole-animal perspective, do not make IL-17. We have found that the purple sea urchin larva, which has a simple gut but is more closely related to humans, makes IL-17 exclusively in the cells that make up the gut, and also makes several other regulators known to be important in gut immunity in humans. We would like to use this larval model to study the regulatory interactions between IL-17 and other important genes in the gut epithelium, and how these genes work together to coordinate immunity and inflammation in the intestines. This knowledge will make it much easier to understand and treat human diseases.

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