Resolving gene-environment interactions in IBD via AHR. - Kenneth Rainin Foundation

Resolving gene-environment interactions in IBD via AHR.

In 1848, a German philosopher, Ludwig Feuerbach, first used the phrase “We are what we eat.” This famous statement is particularly true in Inflammatory Bowel Disease (IBD) where a western diet lacking in plant derived components is a well-recognised risk factor. However, we still do not understand how the food we eat can contribute to IBD. It is clear that diet alone does not cause IBD. Instead, people also need to carry genetic risk factors. Unfortunately, nobody knows how genetics and diet interact to cause IBD. 

Crucially, there is a gene, called AHR, that is both an important sensor of dietary compounds and an IBD risk factor. This provides a unique chance to study how diet and genes interact in IBD. We have found that AHR probably contributes to IBD through effects in an important immune cell, called macrophages. However, exactly what AHR does in macrophages is unknown. Our proposal brings together two labs at the Francis Crick Institute, one that specifically works on AHR and one that specifically works on IBD genetics in immune cells. Together, we will investigate what AHR is doing in macrophages, and intend to figure out how this goes wrong in IBD.