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

This is the authors' abstract. We don't add key points for this paper.

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 organisation, exerting crucial roles in multiple physiological processes. Here, we report a novel mechanism underlying cell polarity and uropod retraction. We demonstrate that galectin-9 regulates chemokine-driven and basal DC migration both in humans and mice, indicating a conserved function for this lectin. We identified the underlying mechanism, namely a deficiency in cell rear contractility mediated by galectin-9 interaction with CD44 that in turn regulates RhoA activity. Analysis of DC motility in the 3D tumour-microenvironment revealed galectin-9 is also required for DC infiltration. Moreover, exogenous galectin-9 rescued the motility of tumour-immunocompromised human blood DCs, validating the physiological relevance of galectin-9 in DC migration and underscoring its implications for DC-based immunotherapies. Our results identify galectin-9 as a necessary mechanistic component for DC motility and highlight a novel role for the lectin in regulating cell polarity and contractility.