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Integrin α4β1; Integrin α4β7 (α4β1 (for very late antigen-4, VLA-4); α4β7 (for lymphocyte Peyer’s patch adhesion molecule-1, LPAM-1))
- Target
- α4β1 (for very late antigen-4, VLA-4); α4β7 (for lymphocyte Peyer’s patch adhesion molecule-1, LPAM-1)
- Molecular classification
- Integrin family, Cell adhesion receptor, Transmembrane receptor
01
Overview
Integrin α4β1 (VLA-4) and integrin α4β7 (LPAM-1) are heterodimeric cell surface receptors composed of distinct alpha (α4) and beta (β1 or β7) subunits. These integrins are expressed on various leukocytes and are fundamental for their migration, trafficking, activation, and survival. Integrin α4β1 primarily mediates adhesion and migration to sites of inflammation via binding to VCAM-1 and fibronectin, while α4β7 promotes lymphocyte homing to the gut through binding to MAdCAM-1. Both receptors play key roles in immune surveillance, inflammation, and metastasis, and are proven therapeutic targets in diseases such as multiple sclerosis, Crohn’s disease, and certain cancers. Their function depends on conformational activation, ligand specificity, and dynamic regulation by chemokines and cytokines[1][3][5].
- Other names
- Very late antigen-4 (VLA-4)Lymphocyte Peyer’s patch adhesion molecule-1 (LPAM-1)
02
Mechanism of action
Blockade of integrin-ligand interaction, thereby inhibiting leukocyte adhesion and migration to inflamed/infected/tumor tissues Prevention of T cell transmigration across blood–brain barrier or into gut mucosa
03
Biological functions
Leukocyte adhesionCell migration, including homing of lymphocytes to tissuesCell traffickingImmune response
04
Disease associations
Inflammation (autoimmune diseases such as multiple sclerosis, allergic conjunctivitis, asthma, sarcoidosis, encephalitis)Cancer (metastasis, tumor cell migration)Infection
05
Safety considerations
Risk of progressive multifocal leukoencephalopathy (PML) with natalizumab due to immunosuppressionGeneral risk of immunosuppression and increased infection susceptibilityGut-specific blockade may reduce systemic safety concerns (example: vedolizumab primarily affects mucosal immunity)
06
Interacting drugs
Natalizumab (targets α4 integrins, especially α4β1 and α4β7, used in multiple sclerosis and Crohn’s disease)
2 more in the full profile.
07
Biomarkers
Expression of α4β1 or α4β7 on immune cell subsets (e.g., memory CD4+ T cells, B cells, gut-homing lymphocytes)MAdCAM-1 expression in gut tissue (for α4β7)VCAM-1 expression on endothelium (for α4β1)
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