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

Guus A Franken1, Harry Warner1, Jorge Cuenca-Escalona1

  • 1Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, The Netherlands.

The Journal of Cell Biology
|September 23, 2025
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Galectin-9 is crucial for dendritic cell (DC) migration by regulating cell polarity and contractility. This finding has implications for DC-based immunotherapies and understanding immune responses.

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Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Adaptive immunity depends on dendritic cell (DC) migration for antigen transport.
  • Galectins are proteins that regulate cell membrane organization and various physiological processes.

Purpose of the Study:

  • To investigate the role of galectin-9 in regulating DC migration, cell polarity, and uropod retraction.
  • To elucidate the molecular mechanism by which galectin-9 influences DC motility.

Main Methods:

  • Studied DC migration in humans and mice, including basal and chemokine-driven movement.
  • Analyzed RhoA signaling pathways and cell rear contractility upon galectin-9 depletion.
  • Investigated galectin-9 interactions with CD44 and GEF-H1 at the cell surface.
  • Assessed DC recruitment and infiltration in a 3D tumor microenvironment.

Main Results:

  • Galectin-9 depletion impaired DC migration, RhoA signaling, and cell rear contractility.
  • Galectin-9 organizes CD44 at the cell surface, modulating RhoA signaling via GEF-H1.
  • Galectin-9 is essential for DC recruitment and infiltration within the tumor microenvironment.
  • Exogenous galectin-9 restored motility in tumor-compromised human DCs.

Conclusions:

  • Galectin-9 is a key regulator of DC motility by controlling cell polarity and contractility.
  • The findings highlight galectin-9's significance in DC migration and its potential for DC-based immunotherapies.