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Integrin alpha-4 beta-1 and integrin alpha-4 beta-7 are heterodimeric cell adhesion receptors widely expressed on leukocytes and certain precursor cells. The α4β1 heterodimer (VLA-4) interacts primarily with vascular cell adhesion molecule-1 (VCAM-1) and the CS-1 fragment of fibronectin, supporting immune cell migration and costimulation during inflammation. The α4β7 heterodimer (LPAM-1) is specialized for homing lymphocytes to mucosal (gut) tissues via binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Both integrins mediate critical steps in immune surveillance and are validated targets for monoclonal antibody therapeutics in autoimmune diseases. Their activation state is modulated by conformational shifts and metal ion binding, and their expression is induced or upregulated during immune cell activation. Blockade of these integrin-ligand interactions suppresses inappropriate immune cell migration, providing benefit in conditions like Crohn's disease, ulcerative colitis, and multiple sclerosis, but presents infectious and neurologic safety risks.
Blocking integrin-ligand interaction (prevents cell adhesion and migration); Inhibition of lymphocyte trafficking to inflamed tissue; Suppression of immune cell activation; Interference with firm adhesion/extravasation into tissues.
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