Galectin-9 – CD44 interaction (Gal-9/CD44)

Galectin-9 is a tandem-repeat beta-galactoside-binding lectin that interacts with the cell surface glycoprotein CD44 to modulate immune homeostasis and cell trafficking. This interaction is a critical regulator of induced regulatory T cell (iTreg) stability; by binding to CD44, Galectin-9 facilitates the formation of a signaling complex with the TGF-beta receptor I, which enhances Smad3-mediated Foxp3 expression [1, 2]. In oncology, the Galectin-9/CD44 axis is often exploited by tumors to create an immunosuppressive environment, making it a target for checkpoint inhibition to restore anti-tumor immunity [6]. Conversely, in inflammatory and autoimmune conditions such as allergic asthma and rheumatoid arthritis, Galectin-9 acts as a natural inhibitor of the CD44-hyaluronan interaction, thereby reducing pathological leukocyte infiltration and tissue destruction [10, 11]. Therapeutic strategies currently under investigation include monoclonal antibodies to block the interaction in cancer and recombinant Galectin-9 proteins to promote immune tolerance in chronic inflammatory diseases [8, 11].

Other names

Galectin-9/CD44 complexLGALS9-CD44 axisGalectin-9 binding to CD44Ecalectin-CD44 interaction

The interaction is targeted through competitive inhibition of ligand binding, blockade of the protein-protein interface using monoclonal antibodies, or the administration of recombinant Galectin-9 to stabilize regulatory T cells and inhibit hyaluronan-mediated cell migration [10, 11].