The enteric nervous and immune systems: interactions for mucosal immunity and inflammation

A number of anatomical studies have demonstrated the presence of peptidergic nerve fibers infiltrating mucosal lymphoid tissues. The exact mechanisms of how neuropeptides are released to affect these lymphoid sites are unclear, but radiolabeled binding studies have shown that mucosal leukocytes bear a number of neuropeptide receptors on their cell surfaces capable of responding to neural signals. The presence of neuropeptide-containing fibers and the ability to receive neural signals suggest that mucosal lymphocytes can be influenced by neurogenic mediators. The objectives set forth in this review are to provide what is currently known about the ability of substance P and vasoactive intestinal peptide to promote mucosal IgA responses in the gastrointestinal tract via Th2 mechanisms and to discuss how these neuropeptides contribute to the exacerbation of the inflammatory diseases of the gastrointestinal tract. We describe how immune responses develop in the gastrointestinal immune system and emphasize how neuropeptides may influence the differentiation of lymphocytes in mucosal inductive tissues and their subsequent expression in mucosal effector sites. Finally, we discuss new techniques developed by the Mucosal Immunization Research Group that have enabled the study of mucosal immune responses.