Intestinal epithelial pathobiology: past, present and future.

The intestinal epithelium serves as one of man's primary interfaces with the outside world. Its importance is illustrated by the fact that the proper functioning of this interface is absolutely essential for human health, and even modest perturbations in its function may lead to diarrhoea, constipation, malnutrition, dehydration, infectious disease or chronic intestinal inflammatory diseases such as Crohn's disease and ulcerative colitis, collectively referred to as inflammatory bowel disease. Both pathogen-induced intestinal inflammation and the active flares of inflammatory bowel disease are histopathologically defined, their sequellae being mediated by neutrophils that migrate across the intestinal epithelium, forming a crypt abscess. Classically, the intestinal epithelium has been thought of primarily as a barrier, and indeed this is a very important aspect of its function, but the intestinal epithelium is also a highly interactive barrier. This chapter will summarize some of the basic research conducted over the past 15 years that has revealed basic insights into how the epithelium participates in the formation of a crypt abscess and how it plays a role in causing the characteristic clinical manifestations that ensue. In addition, the chapter will discuss how this research has resurrected the 'old', yet newly emerging, concept that physiological malfunction of the intestinal epithelium can be the primary defect that leads to the innate and adaptive immune dysregulation mediating inflammatory bowel disease.