Integrin subunit alpha L (ITGAL) (ITGAL)

Integrin subunit alpha L (ITGAL), also known as CD11a, is a transmembrane protein that non-covalently pairs with the integrin beta 2 subunit (CD18) to form the heterodimeric receptor Lymphocyte Function-associated Antigen-1 (LFA-1). LFA-1 is expressed exclusively on the surface of leukocytes and plays a fundamental role in the immune response by mediating cell-cell adhesion through its interaction with Intercellular Adhesion Molecules (ICAMs), particularly ICAM-1. This interaction is critical for the firm arrest of leukocytes on the vascular endothelium, their subsequent extravasation into tissues, and the formation of the immunological synapse between T cells and antigen-presenting cells. Dysregulation of LFA-1 activity is associated with various inflammatory and autoimmune disorders, including dry eye disease, psoriasis, and systemic lupus erythematosus. Consequently, Integrin alpha L is a significant therapeutic target; for instance, the small molecule antagonist Lifitegrast is used to treat dry eye disease by blocking the LFA-1/ICAM-1 interaction. Historically, the monoclonal antibody Efalizumab was used for psoriasis but was withdrawn due to safety concerns regarding progressive multifocal leukoencephalopathy. Ongoing research continues to explore LFA-1 inhibition as a strategy for managing chronic inflammation and preventing transplant rejection.

Other names

CD11aIntegrin alpha LLFA-1 alphaLFA1ALymphocyte function-associated antigen 1 alpha subunit

Drugs targeting Integrin alpha L primarily act as antagonists that block the interaction between the LFA-1 heterodimer and its ligands, such as ICAM-1. This inhibition prevents the firm adhesion of leukocytes to the endothelium, reduces their recruitment to inflammatory sites, and disrupts the formation of the immunological synapse, thereby dampening the inflammatory response.