The immunological and genetic basis of inflammatory bowel disease.
The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. Enormous progress has been made recently in understanding the pathogenesis of these diseases. Through the study of patients and mouse models, it has emerged that Crohn's disease is driven by the production of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma), whereas ulcerative colitis is probably driven by the production of IL-13. A second area of progress is in the identification of specific genetic abnormalities that are responsible for disease. The most important finding is the identification of mutations in the gene that encodes NOD2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. Here, we discuss these recent findings and the implications for therapy.
Bouma
Gerd
G
The Mucosal Immunity Section, National Institutes of Health, Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institutes of Allergy and Infectious Diseases, 10 Center Drive, Room 11N238, Bethesda, Maryland 20892, USA.
Strober
Warren
W
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D007108:Immune Tolerance; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D002352:Carrier Proteins; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein