CERVO Brain Research Centre, Université Laval, Québec, QC, G1J 2G3, Canada.
Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, 2601 Chemin de la Canardiere, Québec, QC, G1J 2G3, Canada.
Mol Neurobiol. 2019 Sep;56(9):6371-6385. doi: 10.1007/s12035-019-1527-0. Epub 2019 Feb 23.
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.
半乳糖凝集素-3（Gal-3）是一种β-半乳糖苷结合凝集素，最近被认为是一种具有免疫调节功能的分子。我们研究了 Gal-3 在生理条件下和缺血性损伤情况下对小胶质细胞形态、迁移和分泌谱的影响。我们发现，在对照条件下，重组 Gal-3 通过 IL-4 依赖的机制增加体外和体内小胶质细胞的分支和运动。重要的是，中风后，Gal-3 表现出明显的免疫调节特性。在大脑中动脉闭塞（MCAO）后 24 小时给予 Gal-3 与 Ym1 阳性小胶质细胞增加和 iNOS 减少有关。在 i.c.v. 注射 Gal-3 24 小时后，对细胞因子谱进行蛋白质水平分析显示，促炎细胞因子下调，抗炎细胞因子 IL-4 明显上调。重要的是，小胶质细胞中观察到的细胞因子变化与梗死面积的显著减少有关。总之，我们的结果表明，当在缺血性损伤后给予 Gal-3 时，它可能会微调先天免疫，并诱导小胶质细胞极化的治疗性转变。
