Update in inflammatory bowel disease pathogenesis

Abstract

Purpose of review: During the last few years, significant advances have been achieved in the understanding of the pathogenesis of inflammatory bowel disease (IBD). By gaining new insights, paradigms that seemed to be a safe basis of our knowledge on IBD pathogenesis have recently become doubtful. This review discusses and summarizes the most recent developments.

Recent findings: Important new insights have been gained into the function of caspase-activating and recruitment domain-15 (CARD15)/NOD2, the first cloned susceptibility gene for Crohn disease (CD). New data on CARD15/NOD2 function and nuclear factor-kappaB activation indicate that an inflammatory reaction of the intestinal mucosa as a response of the innate immune system may be necessary for the maintenance of gut homeostasis. CD may therefore be seen as a defective immune response, no longer only as hyperresponsiveness of the mucosal immune system. Data on CARD15/NOD2 expression suggest that macrophages and epithelial cells could be the site of a primary pathophysiologic defect, and T-cell activation might just be a secondary effect inducing chronification of the inflammation, perhaps as a backup mechanism to a defective innate immunity. In addition to CARD15/NOD2, there are additional "innate" pathways by which commensal and pathogenic bacteria can directly interact with cells of the intestinal mucosa (eg, toll-like receptors). The "germ concept" and the "genetic concept" of IBD pathophysiology are converging.

Summary: New findings are changing our concepts of the pathogenesis of IBD. The innate immune system, early responses to bacterial products, and the modulation of T-cell responses are important aspects that are reviewed.