Functional consequences of neuroimmune interactions in the intestinal mucosa

A single layer of epithelial cells lines the gastrointestinal tract forming a critical first-line barrier between the external environment and the body proper. Acute changes in epithelial physiology (e.g. increased fluid secretion to wash away noxious substances), mediated by neuroendocrine or immune signals, are necessary and beneficial to host defence against enteric pathogens and other threats from the intestinal lumen. However, an inability to down-regulate this response may lead to pathophysiological events. In this chapter, we will review the structure and function of the intestinal epithelium, and present recent advances in the understanding of neuroimmunophysiology of the intestinal mucosa. Because of the wealth of literature in the area, we will emphasize the interaction between enteric nerves and mucosal mast cells in the regulation of epithelial function. It has become clear that the role of mast cells in the intestinal mucosa is not only to react to antigens via bound IgE antibodies, but also to actively control the barrier and transport properties of the epithelium. Studies in animal models of food allergy, nematode infections, and stress have provided evidence that changes in mucosal physiology are due to the direct action of mast cell mediators on epithelial receptors and/or indirect action via nerves/neurotransmitters. Moreover, chronic activation of mast cells in models of hypersensitivity and stress suggest a role for mast cells in initiating mucosal inflammation. There is also mounting evidence for the importance of nerve-mast cell interactions in gastrointestinal diseases in humans. An increased understanding of the mechanisms involved in pathogenic events may lead to new treatment modalities for various gastrointestinal disorders.