Blocking Lymphocyte Localization to the Gastrointestinal Mucosa as a Therapeutic Strategy for IBD

摘要

Lymphocyte migration (homing) to specific tissues has an important role during protective and pathological immune responses, including inflammatory bowel diseases (IBDs). Lymphocytes use integrin α4β7 and the chemokine receptor CCR9 to localize to the gastrointestinal (GI) mucosa; their respective ligands, MAdCAM-1 and CCL25, are displayed on endothelial cells in intestinal post-capillary venules. Whereas GI-homing receptors are required for lymphocyte migration to the intestine in the non-inflamed steady state, their role during inflammation is a matter of debate. Reagents designed to block interactions between these receptors and their ligands have had variable degrees of success in animal models of IBD and patients. We discuss the mechanisms involved in lymphocyte localization to the intestinal mucosa and how they can be applied to therapy for IBD.