Integrin alpha 4 beta 1
Integrin alpha 4 beta 1, known as VLA-4 and composed of the CD49d and CD29 subunits, is the key leukocyte integrin controlling lymphocyte trafficking into inflamed tissue. Expressed on lymphocytes, monocytes, eosinophils and basophils but not on neutrophils, it binds VCAM-1 on cytokine-activated endothelium and the CS-1 splice segment of fibronectin, supporting rolling, firm arrest and transmigration. The receptor also participates in lymphocyte costimulation and in retaining hematopoietic progenitors within the bone marrow niche. Because alpha 4 beta 1 mediates pathogenic leukocyte entry into the central nervous system and gut, it is the target of natalizumab, an approved therapy for relapsing multiple sclerosis and Crohn disease, making this heterodimer one of the best-validated adhesion drug targets.
