First line of defense: the role of the intestinal epithelium as an active component of the mucosal immune system

Over the past decade, many studies have revealed the immunological importance of IECs, not only in maintaining a physical barrier to the external environment but also by functioning alongside cells of the immune system to prevent infection and epithelial injury (summarized in Fig. 1). Intestinal epithelial cells secrete a variety of extrinsic factors, ranging from those which facilitate repair of damaged tissue, such as ITF, to mucin and anti-microbial peptides which directly inhibit bacterial growth across the epithelial monolayer. In addition to those mechanisms which are reliant upon the inherent properties of the epithelium, IECs also function by directly influencing local immune responses. Through the expression of adhesion molecules, costimulatory factors, and a vast array of cytokines, epithelial cells can affect such processes as leukocyte infiltration and IEL growth, development, and responsiveness to antigenic stimuli. The intestinal epithelia may also play a role in processing and presenting luminal antigens to adjacent lymphocyte populations, thereby directing immune responses to specific foreign agents to which the monolayer is exposed. The combination of epithelial cell properties so far described implicates IECs as cells crucial in maintaining the intestinal mucosa in a constant state of immune responsiveness. IECs can be thus defined as essential components of the mucosal immune system.