Genes regulating autophagy in Chron's disease

Crohn’s disease (CD) is one of the two forms of inflammatory bowel disease. CD is a chronic disorder leading to relapsing intestinal inflammation of the gastrointestinal tract. The onset of the CD is multifactorial determined by a combination of four factors. These factors are persistent infections (e.g. adherent-invasive Escherichia coli), dysbiosis of protective and aggressive commensal species, defective mucosal barrier and a dysregulated immune response. In this study the focus is on the process of autophagy because this is one of the factors that dysregulate the immune response. Autophagy protects the cell from invasion of intracellular pathogens and controls inflammation. Three genes are linked with autophagy in CD, these are Nod2, ATG16L1 and IRGM. Normally Nod2 seems to induce autophagy by recruiting ATG16L1 to the bacterial entry site; ATG16L1 initiates autophagy by recruiting ATG5 and ATG12 proteins on the developing phagophore and IRGM binds with GTP to generate the autolysosome. The CD-associated variants of Nod2, ATG16L1 and IRGM seem to cause a less effective response to pathogens and they could be a trigger for the immune system to react to commensal bacteria. Thus, immunity is disturbed in CD. Also autophagy seems to have an effect on replication and/or growth of adherent-invasive Escherichia coli bacteria.