Integrin and mucosal vascular addressin cell adhesion molecule

Integrins on the surface of leucocytes can bind to specific molecules on other cells to facilitate “immune cell homing” (Currò et al., 2017). In IBD, leucocytes bearing the α4β7 integrin selectively bind to the mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), which is expressed in the gut (Bravatà et al., 2015). The process is facilitated by MAdCAM-1 expression being upregulated by pro-inflammatory cytokines released from activated T cells that have migrated to gastrointestinal mucosa (Bravatà et al., 2015).

Video 2: Animation outlining the role of integrin α4β7-MAdCAM-1 binding in IBD (Bravatà et al., 2015).

Inhibiting the binding of α4β7-bearing leucocytes to MAdCAM-1 may provide selective IBD therapy and is currently approved for the treatment of certain patients with moderate or severely active Crohn’s disease or ulcerative colitis (Currò et al., 2017; Entyvio SmPC, 2018). Note that this is not the only target for integrins and adhesion molecules in IBD, and leucocyte trafficking may also be targeted with other integrin–ligand combinations (Bravatà et al., 2015; Coskun et al., 2017).