Morphological relationships between peptidergic nerve fibers and immunoglobulin A-producing lymphocytes in the mouse intestine

Immunoglobulin A (IgA) lymphocytes are present close to the nerve fibers in the lamina propria of the small intestine, and the administration of lipopolysaccharides (LPSs) increases the number of these cells and IgA secretion to the lumen. In the present study, we demonstrated that the nerve fibers immunoreactive for vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) were close to the IgA lymphocytes in the mouse ileum lamina propria. Three hours after intraperitoneal administration of LPSs, IgA lymphocytes close to VIP nerve fibers, those close to basement membrane, and those close to both VIP nerve fibers and basement membrane were increased in number. Further, all IgA lymphocytes seen in the ileum lamina propria expressed the receptors for VIP, VIPR1, and VIPR2. Electron microscopy revealed that varicosities were in close apposition to the lymphocyte plasma membrane. The present study suggests that VIP/NPY/CGRP neurons in the submucosal plexus have a close anatomical relationship to IgA lymphocytes, playing a role in the secretion of IgA and intestinal fluid in response to stimulation by lipopolysaccharides, pathogens, or toxins.