Grant: Project Grant

Inflammatory bowel diseases (IBD) affect 1 in 150 Canadians, one of the highest incidences worldwide. Risk factors include genetic predisposition, smoking, hygiene, diet, gut pathogens, and environmental factors, including sun exposure. Extensive public health data have revealed an inverse relationship between incidence of Crohn's disease, latitude and sun exposure. Notably, moderate exposure of skin to UV irradiation produces a molecule called FICZ, which can activate the aryl hydrocarbon receptor (AhR). The AhR is abundant in several organs, including the gut, and is implicated in protection against IBD. The capacity of the AhR to be activated by molecules of dietary and environmental origin may be key to its protective actions in IBD. We have compelling evidence that molecules produced in skin by moderate UV exposure activate the AhR in several peripheral organs including the gut and influence immune signaling. The core goals of this application are to understand the consequences of activation of the AhR by UV light on intestinal immunity and how this protects against IBD. We will also study the effects of activation of the AhR on microbial components of the gut. Our working hypotheses are that (i) moderate UV exposure produces molecules that act to reinforce immune signaling by the AhR in peripheral organs, and (ii) that AhR signaling induced by cutaneous UV exposure influences the microbial composition of the intestine. These studies provide a mechanistic link between sun exposure and reduced incidence of IBD.