Can gene-environment interaction in Paneth cells trigger Crohn's disease?

Crohn's disease is a debilitating disease diagnosed at two peaks of age – in early adulthood, and in the sixth to seventh decade of life. It causes profound, life-long suffering and remains a major unmet medical need. Amongst immune-related diseases, Crohn's disease is special in that very few risk genes account for a huge fraction of its heritability. During his award, Professor Kaser will test the hypothesis that a genetically affected, relatively coherent biological mechanism operative in Paneth cells might determine the characteristic features of Crohn's disease involving the ileum. This mechanism would interact with more 'generic' genetically affected pathways, associated with increased immune reactivity and/or decreased tolerance, shared with other immune diseases. Delineation of such a mechanism will allow the predicting and testing of which environmental triggers set off ileal Crohn’s disease in genetically susceptible individuals. Together with studies in genetically stratified patient samples, Professor Kaser believes this affords an unparalleled opportunity to gain fundamental insights into Crohn’s disease, with the aim of informing a precise therapeutic intervention.