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Delayed Galectin-3-Mediated Reprogramming of Microglia After Stroke is Protective

  • Reza Rahimian
  • Starlee Lively
  • Essam Abdelhamid
  • Melanie Lalancette-Hebert
  • Lyanne Schlichter
  • Sachiko Sato
  • Jasna KrizEmail author
Article
  • 151 Downloads

Abstract

Galectin-3 (Gal-3), a β-galactoside-binding lectin, has recently emerged as a molecule with immunoregulatory functions. We investigated the effects of Gal-3 on microglia morphology, migration, and secretory profile under physiological conditions and in the context of ischemic injury. We show that in the control conditions, exposure to recombinant Gal-3 increases microglial ramification and motility in vitro and in vivo via an IL-4-dependent mechanism. Importantly, after stroke, Gal-3 exerted marked immune-modulatory properties. Delivery of Gal-3 at 24 h after middle cerebral artery occlusion (MCAO) was associated with an increase in Ym1-positive microglia and decrease in iNOS. Analysis of cytokine profiles at the protein level revealed downregulation of pro-inflammatory cytokines and a marked upregulation of the anti-inflammatory cytokine, IL-4, 24 h after i.c.v. injection of Gal-3. Importantly, the observed shift in cytokines in microglia was associated with a significant decrease in the infarct size. Taken together, our results suggest that when delivered well after ischemic injury, Gal-3 might fine tune innate immunity and induce a therapeutic shift in microglia polarization.

Keywords

Galectin-3 Microglia Interleukin 4 Stroke Innate immunity 

Notes

Funding

This work was supported by the Heart and Stroke Foundation of Canada Grant-in Aid no. G-17-0018372 (J.K.)

Compliance with Ethical Standards

All experimental procedures were approved (protocol no. 017-133) by the Laval University Animal Care Ethics Committee and are in accordance with the Canadian Council on Animal Care.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2019_1527_MOESM1_ESM.pdf (272 kb)
ESM 1 (PDF 271 kb)

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Authors and Affiliations

  1. 1.CERVO Brain Research CentreUniversité LavalQuébecCanada
  2. 2.Krembil Research InstituteUniversity Health NetworkTorontoCanada
  3. 3.Glycobiology Laboratory, Research Centre for Infectious DiseaseUniversité LavalQuebecCanada
  4. 4.Department of Psychiatry and Neuroscience, Faculty of MedicineUniversité LavalQuébecCanada

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