Understanding the mechanisms that drive uncontrolled inflammation in Crohn's disease (CD) remains one of the most pressing challenges in contemporary experimental medicine. Recently, a three-phased view on the pathogenesis of CD was proposed in which following the breakdown of intestinal epithelial barrier function, CD patients fail to clear the resulting infectious debris, provoking subsequent immune responses. This view on CD is attractive in that it is testable and allows better diagnosis of disease if proven correct, apart from opening a window on new therapeutic horizons. Here we shall argue, however, that this scheme may be an oversimplification in that it ignores the genetic diversity of CD and thus does not fully take into account the nature of the intestinal epithelium, which appears a non-passive actor in this disease.
Keywords: Crohn’s disease (CD); epithelial barrier; innate immunity; risk gene.