Target intelligence / Profile preview

Lymphocyte function-associated antigen 1 (Integrin alpha-L beta-2) (LFA-1)

Target
LFA-1
Molecular classification
Integrin, Receptor, Cell adhesion molecule
01

Overview

Lymphocyte function-associated antigen 1 (LFA-1) is a heterodimeric integrin receptor composed of CD11a (ITGAL) and CD18 (ITGB2) subunits, primarily expressed on the surface of leukocytes (Source: UniProt P20333). It plays a critical role in the immune system by binding to its ligand, Intercellular Adhesion Molecule 1 (ICAM-1), which facilitates leukocyte adhesion to the endothelium, transendothelial migration, and the formation of the immunological synapse (Source: PubMed 18425118). In the specific context of bone marrow-derived human mesenchymal stem cells (BM-hMSCs), the interaction between LFA-1 on immune cells and ICAM-1 on MSCs is essential for the immunosuppressive activity of MSCs, as it allows for stable cell-to-cell contact and subsequent paracrine signaling (Source: PubMed 18272601). Dysregulation of the LFA-1/ICAM-1 pathway is implicated in various inflammatory and autoimmune disorders, including psoriasis and dry eye disease. Therapeutic targeting of LFA-1 involves small molecules like lifitegrast or monoclonal antibodies like efalizumab that block the LFA-1/ICAM-1 interaction to reduce pathological inflammation (Source: PubChem CID 11617559). While effective, such therapies must be monitored for potential safety concerns, including an increased susceptibility to infections and, in rare cases, progressive multifocal leukoencephalopathy (Source: FDA).

Other names
CD11a/CD18Integrin alpha-L beta-2ITGAL/ITGB2LFA1CD11aCD18
02

Mechanism of action

LFA-1 antagonists bind to the integrin and prevent its interaction with ICAM-1, thereby inhibiting leukocyte recruitment, adhesion to vascular endothelium, and activation of T-lymphocytes (Source: FDA, Lifitegrast Label). In the context of MSCs, this interaction facilitates the proximity required for MSC-mediated immunosuppression (Source: PubMed 18272601).

03

Biological functions

Cell adhesion (Source: UniProt P20333)Immune response (Source: PubMed 18425118)Leukocyte migrationSignal transductionImmunological synapse formationT-cell activation
04

Disease associations

InflammationAutoimmune diseaseDry eye syndrome (Source: FDA)PsoriasisGraft-versus-host diseaseTransplant rejection
05

Safety considerations

Increased risk of infectionProgressive multifocal leukoencephalopathy (PML) (Source: FDA, Efalizumab safety alert)Hypersensitivity reactionsImmunosuppression
06

Interacting drugs

Lifitegrast

3 more in the full profile.

07

Biomarkers

CD11a expressionICAM-1 expressionSoluble ICAM-1 (sICAM-1)T-cell activation markers

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