Galectin-9 regulates dendritic cell contractility and migration via RhoA

Franken, G.; Cuenca-Escalona, J.; Stehle, I. F.; van Reijmersdal, V.; Gokhale, R. R.; Classens, R.; diBlasio, S.; Rodgers Furones, A.; Dolen, Y.; van Spriel, A.; Querol Cano, L.

doi:10.1101/2023.10.30.564706

bioRxiv · 10.1101/2023.10.30.564706

Galectin-9 regulates dendritic cell contractility and migration via RhoA

Franken, G.·Cuenca-Escalona, J.·Stehle, I. F.·van Reijmersdal, V.·Gokhale, R. R.·Classens, R.·diBlasio, S.·Rodgers Furones, A.·Dolen, Y.·van Spriel, A.·Querol Cano, L.

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Abstract

Adaptive immunity relies on dendritic cell (DC) migration to transport antigens from tissues to lymph nodes. Galectins, a family of {beta}-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.

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Franken, G., Cuenca-Escalona, J., Stehle, I. F., van Reijmersdal, V., Gokhale, R. R., Classens, R., diBlasio, S., Rodgers Furones, A., Dolen, Y., van Spriel, A., Querol Cano, L.. 2023-11-01. Galectin-9 regulates dendritic cell contractility and migration via RhoA. https://doi.org/10.1101/2023.10.30.564706

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