MADCAM1

MAdCAM-1, or mucosal addressin cell adhesion molecule-1, is a cell-surface adhesion molecule of the immunoglobulin superfamily. It is expressed primarily on the endothelium of gut-associated lymphoid tissue, notably on high endothelial venules in the intestinal lamina propria and Peyer's patches. MAdCAM-1 serves as the ligand for the integrin α4β7 on circulating lymphocytes, and its interaction mediates the selective homing of gut-tropic T and B cells to the intestinal mucosa. This trafficking supports mucosal immune surveillance and responses to gut antigens.

Structure and regulation: MAdCAM-1 is a single-pass type I transmembrane glycoprotein with extracellular immunoglobulin-like domains that bind α4β7. The extracellular region contains two Ig-like domains, followed by a transmembrane segment and a cytoplasmic tail that participates in signaling and endocytosis. The molecule is N-glycosylated, and its expression on gut HEVs can be upregulated in inflammatory states, contributing to enhanced lymphocyte recruitment during mucosal inflammation.

Clinical and research relevance: MAdCAM-1’s role in directing lymphocyte homing to the gut makes it a focus in inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. Therapies that disrupt the MAdCAM-1–α4β7 interaction can reduce gut-directed lymphocyte trafficking; for example, targeting the α4β7 integrin with biologics like vedolizumab indirectly interferes with this axis. Anti-MAdCAM-1 antibodies have also been explored in research settings. Beyond therapy, MAdCAM-1 is used as a histological marker for identifying gut-associated HEVs in immunology studies.