Review article: Homing of mucosal immune cells--a possible connection between intestinal and articular inflammation

An adaptive immune system has developed to protect mucosa, mainly by performing immune exclusion with secretory antibodies (SIgA and SIgM) but also by downregulating pro-inflammatory antibody responses and delayed type hypersensitivity against harmless soluble proteins and the indigenous bacterial flora. In general, mucosal immunopathology appears to represent abrogation of such mucosal tolerance mechanisms. An important consequence is disturbance of the 'gatekeeper' function normally performed by the microvasculature through complementary sets of tightly regulated adhesion molecules on mucosal endothelium and circulating leukocytes. The B cells responsible for local polymeric immunoglobulin (Ig) production (mainly dimeric IgA) are stimulated initially in organized lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine, from which they migrate as memory cells to secretory tissues all over the body. Mucous membranes are thus furnished with primed B cells in an integrated way, ensuring a variety of secretory antibody specificities at every exocrine site. There is currently great interest in exploiting this integrated or 'common' mucosal immune system for topical vaccination against pathogenic infectious agents and also to induce therapeutic peripheral tolerance to ameliorate T-cell-mediated autoimmune diseases. Moreover, homing of immune cells from the gut to the inflamed synovium may represent a modifiable link between intestinal immunity and chronic arthropathies.