CD49d

CD49d, also known as integrin alpha-4, is a transmembrane glycoprotein that forms part of the integrin family. It is encoded by the ITGA4 gene and serves as the alpha subunit in heterodimeric integrins that mediate cell adhesion. The alpha-4 subunit pairs with beta-1 to form VLA-4 (very late antigen-4) and with beta-7 to form α4β7 (LPAM-1). These receptors enable leukocyte interactions with vascular endothelium and extracellular matrix.

Ligands and function: The primary ligands for CD49d-containing integrins are vascular cell adhesion molecule-1 (VCAM-1) on activated endothelium and the CS1 region of fibronectin. Through these interactions, CD49d-containing integrins regulate leukocyte adhesion, rolling, and transmigration into tissues, playing a key role in immune surveillance and inflammatory responses. Expression of CD49d is broad among leukocytes, including T cells, B cells, natural killer cells, monocytes, and eosinophils, with varying levels depending on cell type and activation state. In addition to mediating adhesion, CD49d participates in immunological synapse formation and may influence cell migration within tissues.

Clinical relevance: Because CD49d is central to leukocyte trafficking, its function is a therapeutic target. Antagonists of alpha-4 integrins, such as natalizumab, inhibit CD49d-containing integrins to reduce inflammatory cell migration and are approved for conditions like multiple sclerosis and Crohn’s disease. These therapies carry risks, including the potential for progressive multifocal leukoencephalopathy, necessitating careful patient monitoring. In research and diagnostics, anti-CD49d antibodies are used to identify and characterize leukocyte subsets by flow cytometry.