The Role of the Epithelial Barrier in Inflammatory Bowel Disease
Edward E.S. Nieuwenhuis and Richard S. Blumberg
Inflammatory Bowel Diseases (IBD) represent a heterogeneous group of diseases with two distinct disorders of unknown etiology, Crohn’s disease (CD) and ulcerative colitis (UC).
Both diseases are characterized by chronic intestinal inflammation. Genetic susceptibility, environmental triggers and immune dysregulation have been described as the main factors involved in the establishment and development of IBD.1 One hypothesis on the etiology of IBD is that these diseases represent an aberrant immune response by the mucosal immune system, to either pathogenic or resident luminal bacteria.2 According to this hypothesis, resident bacteria can persistently stimulate the mucosal and systemic immune system, thereby perpetuating the inflammatory response. This hypothesis is supported by the recent evidence of a mutation of the bacterial sensing gene NOD2 being strongly associated with susceptibility to CD.3,4 The importance of luminal bacteria in the pathogenesis of IBD draws particular attention to the role played by the intestinal epithelial cell. In addition to their important barrier, absorption, and transport function, intestinal epithelial cells (IEC) play an important role in innate and adaptive immune functions including management of the luminal microbial ecology. The inducible secretion of regulatory molecules by IEC is consistent with the notion that these cells may play a role in initiating and regulating physiologic and pathological mucosal responses, associated with the development of IBD. Moreover, the IEC may be an important target of the dysregulated immune response, due to the effects of either barrier disruptive cytokines (IFN-g, IL-14, IL-13, TNF-a) and cytotoxic T cells, which may further enhance inflammation and prevent appropriate repair processes.