New insights into the pathogenesis of Crohn's disease: are they relevant for therapeutic options?
During the last few years significant advances have been achieved in the understanding of the pathogenesis of inflammatory bowel disease (IBD). A genetic susceptibility to Crohn's disease has been proven by identification of variations as risk factor NOD2/CARD15. Functional data on NOD2/CARD15 and NF-kappaB activation indicate that an inflammatory reaction of the intestinal mucosa, as an immediate response of the innate immune system, may be necessary for the maintenance of gut homeostasis. Crohn's disease is now also discussed as an impaired and inadequate immune reaction and no longer only as a hyper-responsiveness of the mucosal immune system. Data on NOD2/CARD15 expression suggest that macrophages and epithelial cells could be the locus of the primary pathophysiological defect and that T-cell activation might just be a secondary effect inducing chronification of the inflammation, perhaps as backup mechanism to insufficient innate immunity. In addition to NOD2/CARD15 there are more "innate" pathways by which commensal and pathogenic bacteria can directly be hindered to invade the human body (such as interaction with Toll like receptors, TLRs and defensins). The "germ-concept" and the "genetic concept" of IBD pathophysiology are converging. However, more time is needed until these important insights in IBD pathogenesis will make their way into routine diagnostic procedures and treatment of patients with IBD.
Vavricka
Stephan R
SR
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital Zürich, Zürich, Switzerland.
Rogler
Gerhard
G
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D023082:Defensins / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D019936:Probiotics / Q000627:therapeutic use; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D023082:Defensins; D016328:NF-kappa B; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D051193:Toll-Like Receptors