NOD2 and Crohn disease: For example, a frame-shift mutation of NOD2 was associated with the development of Crohn’s disease in a study of over 400 unrelated subjects (8), and in experimental colitis, a NOD2 deficiency exacerbated disease severity due to an uncontrolled immune response leading to immune hyper-responsiveness to intestinal antigens mediated by IL-12-producing antigen-presenting cells (9).