The immunological and genetic basis of inflammatory bowel disease

Abstract

Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract. Although clinically there are some similarities between the two diseases, there are also marked differences. The aetiology of both forms has not been entirely elucidated however, marked progress has been made recently in understanding the immunopathogenesis and genetic susceptibility of these diseases. Through the study of patients and mouse models, it seems that disease occurs as the consequence of a dysregulated immune response to normal constituents of the intestinal flora in a genetically predisposed host. Such mucosal inflammation can be attributed to either increased effector-cell function or decreased regulatory-cell function. Crohn's disease seems to be driven by interleukin-12 (IL-12) and interferon-γ (IFN-γ), whereas a mouse model of ulcerative colitis has been shown to be driven by natural killer T (NKT) cells that produce IL-13. Mutations in the gene encoding the NOD2 (nucleotide-binding oligomerization domain) protein have been identified in a subgroup of patients with Crohn's disease. This opens up the possibility that Crohn's disease is due, at least in some instances, to defects in innate immunity. Recent findings will facilitate the development of new and specific therapies for patients with these diseases.