Integrin alpha-4 beta-7 (α4β7) (α4β7)

Integrin alpha-4 beta-7 (α4β7) is a heterodimeric cell-surface glycoprotein composed of the alpha-4 (CD49d) and beta-7 subunits, primarily expressed on the surface of circulating B and T lymphocytes (UniProt P13612, P26010). It functions as a key mediator of lymphocyte trafficking by binding specifically to mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1), which is predominantly expressed on the vascular endothelium of the gastrointestinal tract (PubMed 24645941). This interaction facilitates the selective homing of leukocytes to the gut-associated lymphoid tissue (GALT) and the intestinal lamina propria. In pathological states such as ulcerative colitis and Crohn's disease, the α4β7-MAdCAM-1 pathway is overactive, leading to chronic inflammation through the excessive recruitment of effector lymphocytes into the gut (PubMed 28433105). Therapeutic targeting of α4β7, using monoclonal antibodies like Vedolizumab or the investigational agent ABBV-382, aims to block this recruitment process (ClinicalTrials.gov NCT04531306). Because MAdCAM-1 expression is largely restricted to the gut, drugs targeting α4β7 provide a gut-selective anti-inflammatory effect. This selectivity minimizes systemic immunosuppression and reduces the risk of opportunistic infections in the central nervous system, a concern seen with non-selective integrin blockers (PubMed 24645941). Consequently, α4β7 is a major therapeutic target for achieving clinical remission in patients with moderate-to-severe inflammatory bowel disease.

Other names

LPAM-1Lymphocyte Peyer's patch adhesion molecule 1Integrin alpha-4 beta-7CD49d/Integrin beta-7α4β7

Antagonist of the interaction between integrin α4β7 and mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1)