Structure and regulation of intestinal epithelial tight junctions: current concepts and unanswered questions

Intestinal epithelium serves as a key interface between internal body compartments and the gut lumen. The epithelial layer forms a physical barrier that protects the body from the harmful environment of the lumen and also mediates vectorial fluxes of fluids, nutrients and waste. Increased permeability of the epithelial barrier is a common manifestation of different gastrointestinal diseases that enhances body exposure to external pathogens thereby exaggerating mucosal inflammation. Barrier properties of the intestinal epithelium are regulated by specialized adhesive plasma membrane structures known as tight junctions (TJs). It is gengrally believed that disease-related increase in intestinal permeability is caused by defects in TJ structure and functions. This chapter describes the molecular composition of intestinal epithelial TJs, basic mechanisms that regulate TJ functions in healthy gut mucosa as well as molecular events that contribute to increased mucosal permeability during intestinal inflammation. The chapter outlines our current understanding of TJ structure and dynamics and highlights several unresolved questions regarding regulation of this junctional complex under normal conditions and in gastroenterological diseases.