Galectin-9 regulates dendritic cell polarity and uropod contraction by modulating RhoA activity.

ABSTRACT: Adaptive immunity relies on dendritic cell (DC) migration to transport antigens from tissues to lymph nodes. Galectins, a family of β-galactoside-binding proteins, control cell membrane organization, exerting crucial roles in multiple physiological processes. Here, we report a novel mechanism underlying cell polarity and uropod retraction by demonstrating that galectin-9 regulates basal and chemokine-driven DC migration in humans and mice. Galectin-9 depletion caused a defect in RhoA signaling that resulted in impaired cell rear contractility. Mechanistically, galectin-9 interacts with and organizes CD44 at the cell surface, in turn modulating RhoA binding to GEF-H1 and the initiation of downstream signaling. Analysis of DC motility in the 3D tumor microenvironment revealed galectin-9 is a

SUBMITTER: Franken GA 

PROVIDER: S-EPMC12456409 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature