The Clinical and Scientific Importance of Mucosal Inflammation

THE CLINICAL AND SCIENTIFIC IMPORTANCE OF MUCOSAL INFLAMMATION Standing at the interface between the host and the environment, mucosal-lined surfaces represent the first line of defense against potential pathogens. This defensive role is particularly relevant to the mucosa of the gastrointestinal tract, the pulmonary system, and the urinary tract, each of which is particularly susceptible to the development of inflammatory diseases due to their role as a barrier that must not only protect, but also serve the physiological function of each of the organ systems. In the case of the gastrointestinal tract, mucosal inflammation is manifest as inflammatory bowel disease (including Crohn’s disease and ulcerative colitis) (1–3) or necrotizing enterocolitis (NEC), a leading cause of death in preterm infants (4). In the case of the pulmonary system, mucosal inflammation may be manifest as pneumonitis, pneumonia, or asthma (5–7), acute and chronic pulmonary conditions that have a high degree of morbidity and potential mortality. And in the case of the urinary tract, mucosal inflammation may be manifest as interstitial nephritis, cystitis, and urethritis (8–10), causes of significant morbidity in patients of all ages. To elucidate the pathogenesis of mucosal inflammatory diseases, research over the past several decades has focused on the role of the immune system in their development— in particular the relationship between mucosal lymphocytes, macrophages, and neutrophils, and the effects of their cellular by-products on mucosal integrity and function (11–13). However, recent work has shed light upon the important role that the epithelia itself may play as a primary regulator of the immune response in the development of mucosal inflammation. No longer an innocent bystander, the epithelial-lined mucosa at each of No Longer an Innocent Bystander: Epithelial Toll-Like Receptor Signaling in the Development of Mucosal Inflammation