Endothelial ligands and homing of mucosal leukocytes in extraintestinal manifestations of IBD

Abstract

Crohn's disease and ulcerative colitis are quite often complicated with manifestations in extraintestinal organs like joints, eye, and skin. Although the etiopathogenesis of these nonmucosal complications remains unsettled, they all share the characteristic feature of inappropriate leukocyte recruitment in nonlymphatic organs. Under normal conditions, lymphocytes recirculate between the blood and lymphoid organs in search of their cognate antigens, whereas polymorphonuclear leukocytes are excluded from tissues. On inflammation, the leukocyte trafficking changes dramatically. Granulocytes infiltrate into the inflammatory focus very rapidly, and they are followed by lymphocytes, especially activated immunoblasts and memory cells, which now also leave the vasculature at nonlymphoid tissues. Leukocyte extravasation from the blood into the tissue is a multistep process governed by sequential interactions between adhesion molecules expressed on the surface of leukocytes and their ligands on the luminal side of the endothelial cells lining the vessels. In this review, we describe the recirculation routes of mucosal lymphocytes in physiologic conditions, as well as the changes seen in mucosal and extramucosal homing in inflammatory bowel disease (IBD). We present a working model of how adhesive molecular interactions between mucosal immune cells and endothelial cells may explain the pathogenesis of the development of inflammatory cell infiltrate in distant organs in IBD, and how this information may help to plan new antiadhesive therapeutic strategies.