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

Integrin alpha 4 beta 1, also known as Very Late Antigen-4 (VLA-4), is a heterodimeric transmembrane receptor composed of the alpha 4 (CD49d) and beta 1 (CD29) subunits. It is predominantly expressed on the surface of various leukocytes, including T and B lymphocytes, monocytes, and eosinophils, where it serves as a critical mediator of cell-cell and cell-extracellular matrix interactions [1, 4, 13]. The primary physiological ligands for this integrin are Vascular Cell Adhesion Molecule-1 (VCAM-1), expressed on activated endothelial cells, and the extracellular matrix protein fibronectin [1, 6, 15]. By facilitating the tethering, rolling, and firm adhesion of leukocytes to the vascular wall, Integrin alpha 4 beta 1 enables the extravasation of immune cells into inflamed tissues, such as the central nervous system in multiple sclerosis or the intestinal mucosa in Crohn's disease [1, 3, 9]. Consequently, it has become a major therapeutic target; drugs like the monoclonal antibody natalizumab block this interaction to reduce pathological inflammation [13, 14]. However, inhibiting this pathway can lead to significant safety concerns, most notably the risk of progressive multifocal leukoencephalopathy (PML) due to impaired immune surveillance against the JC virus [4, 14].

Other names

Very Late Antigen-4VLA-4CD49d/CD29alpha 4 beta 1 integrinITGA4/ITGB1Integrin alpha-4 beta-1

Antagonism of the alpha 4 subunit to block the interaction between alpha 4 beta 1 integrin and its ligands (VCAM-1 and fibronectin), thereby inhibiting leukocyte adhesion and migration into inflamed tissues.