Endogenous Galectin-3 Is Localized in Membrane Lipid Rafts and Regulates Migration of Dendritic Cells

This study reveals a function of endogenous galectin-3, an animal lectin recognizing β-galactosides, in regulating dendritic cell motility both in vitro and in vivo, which to our knowledge is unreported. First, galectin-3-deficient (gal3−/-) bone marrow-derived dendritic cells exhibited defective chemotaxis compared to gal3+/+ cells. Second, cutaneous dendritic cells in gal3−/- mice displayed reduced migration to draining lymph nodes upon hapten stimulation compared to gal3+/+ mice. Moreover, gal3−/- mice were impaired in the development of contact hypersensitivity relative to gal3+/+ mice in response to a hapten, a process in which dendritic cell trafficking to lymph nodes is critical. In addition, defective signaling was detected in gal3−/- cells upon chemokine receptor activation. By immunofluorescence microscopy, we observed that galectin-3 is localized in membrane ruffles and lamellipodia in stimulated dendritic cells and macrophages. Furthermore, galectin-3 was enriched in lipid raft domains under these conditions. Finally, we determined that ruffles on gal3−/- cells contained structures with lower complexity compared to gal3+/+ cells. In view of the participation of membrane ruffles in signal transduction and cell motility, we conclude that galectin-3 regulates cell migration by functioning at these structures.