The relationship between miR-29, NOD2 and crohn’s disease

© Springer International Publishing Switzerland 2015. Crohn’s disease (CD) is a chronic inflammatory bowel disease with a complex aetiology that includes genetic susceptibility and the gastrointestinal microbiome and results in an aberrant Th17 inflammatory response. NOD2 is an intracellular sensor that responds to bacterial cell wall peptidoglycan and contributes to immune defense. Polymorphisms in the NOD2 gene predispose to Crohn’s disease, with the largest effect of any of the known genetic risk factors. We have found that wild-type NOD2 controls the expression of miR-29 in human dendritic cells (DCs). miR-29 regulates the expression of a number of immune mediators including the IL-23 cytokine subunits IL-12p40 and IL-23p19. CD patient DCs expressing NOD2 polymorphisms fail to induce miR-29 and show enhanced IL-12p40 release on exposure to adherent invasive E. coli. Moreover in a murine model deficient in miR-29, a more severe Th17-driven colitis is established after DSS administration. Therefore, we suggest that the loss of miR-29-mediated immunoregulation in CD-variant NOD2 DCs contributes to elevated IL-23 and aberrant Th17 response in this disease.