Integrin alpha-4 beta-1 receptor (VLA-4)

Integrin alpha‑4 beta‑1 receptor, also known as VLA‑4, is a heterodimeric transmembrane protein composed of an alpha 4 subunit (CD49d) and a beta 1 subunit (CD29). It functions primarily as an adhesion receptor mediating interactions between leukocytes and vascular endothelium via binding ligands such as VCAM‑1 on endothelial cells and fibronectin in the extracellular matrix. This interaction plays critical roles in immune cell migration during inflammation by facilitating rolling, firm adhesion, extravasation into tissues, costimulation during immune activation, homing/trafficking/differentiation/survival of various leukocyte subsets. Therapeutically targeting this integrin has proven effective for autoimmune diseases like multiple sclerosis but carries risks related to impaired immune surveillance. The receptor is expressed broadly among hematopoietic lineages except neutrophils; it is essential for embryonic development due to its role in placentation and vascular formation. Drugs such as natalizumab act by blocking ligand binding sites on α₄β₁ integrins.

Other names

VLA-4CD49d/CD29ITGA4/ITGB1Alpha 4 integrinIntegrin α4β1

Blockade of integrin-ligand interaction to inhibit leukocyte adhesion/migration across endothelium. Natalizumab binds α4-integrins on leukocytes, preventing their interaction with VCAM‑1 on endothelial cells. This reduces immune cell infiltration into tissues such as the CNS or gut mucosa.