Crohn’s Disease Susceptibility Locus ITLN1 in Interactions of Commensal Bacteria with Intestinal Epithelia.

Genome wide association studies (GWAS) show that the human gene ITLN1 is associated with Crohn’s disease. A common form of this gene is present in a substantial fraction of individuals with the disease. The functional significance of this association is unknown. A critical step in using genetic information to develop treatments with the potential to benefit patients with Crohn’s disease is figuring out the function of the forms of genes associated with the disease. We propose to test (1) the function of ITLN-1 (the protein produced by ITLN1) in intestine-derived models of Crohn’s disease, focusing on a hypothesis based in large part on our preliminary data showing that ITLN-1 contributes to the interaction of normal gut bacteria with the gut lining; and (2) the role in this process of a particular protein produced by bacteria associated with Crohn’s disease. Insights gained from the proposed studies have the potential to serve as the basis for the development of treatments that could control or prevent illness in individuals carrying Crohn’s disease-associated forms of the ITLN1 gene.