Innervation of mucosal immune cells in the gastrointestinal tract

There is mounting evidence for interactions between the immune and peripheral nervous systems. Many regulatory molecules are candidate mediators for communication between inflammatory cells and nerves; however, the extent of targeting of neurotransmitters (and interleukins) as intersystem messengers has been somewhat overlooked. Lymphoid tissues are well supplied by nerves and the gastrointestinal lamina propria, which is populated by a variety of immune cell types, is densely innervated. One-half to two-thirds of mast cells are closely apposed to nerves in the intestinal mucosa, in both rodents and humans, and nerve stimulation has been reported to cause mast cell activation. Although less extensively studied, both eosinophils and plasma cells in the gastrointestinal mucosa are also positioned for interaction with nerves, and intra-epithelial leukocytes may be subject to diffusible neurally-derived mediators. Peyer's patches are relatively sparsely innervated but appear to express neuropeptide receptors in inflammatory conditions. Although the nerves in the mucosa have traditionally been thought of as a static component, recent experiments suggest that these may undergo extensive remodelling during nematode-induced inflammation. Such data suggest a dynamic interplay between the immune and nervous systems during inflammatory episodes in the gut, although considerable work is still needed to determine the importance of neuro-immune interactions in gastrointestinal homeostasis and inflammation.