Upregulation of Microglial ZEB1 Ameliorates Brain Damage after Acute Ischemic Stroke

Publication date: 27 March 2018
Source:Cell Reports, Volume 22, Issue 13
Author(s): Daojing Li, Wenjing Lang, Chen Zhou, Chao Wu, Fang Zhang, Qiang Liu, Shuang Yang, Junwei Hao
Microglia are a key immune-competent cell type that respond to environmental and physiological changes during ischemic stroke. However, the molecular mechanisms controlling post-ischemic microglia activity are unclear. Understanding these mechanisms may ultimately reduce disease burden and allow the manipulation of microglia responses to shape the outcomes of stroke. Here, we report that, after experimentally induced stroke, ZEB1 is highly expressed in ipsilateral cerebral hemisphere, where it is upregulated mainly in microglia. Using a conditional transgenic mouse, we found that ZEB1 upregulation in microglia regulates immune responses in the CNS and alleviates brain injury after ischemic stroke. Our data indicate that ZEB1 overexpression mediates microglia responses and, in turn, inhibits the production of astrocytic CXCL1 through the TGF-β1-dependent pathway. Reduced CXCL1 leads to a decline in neutrophil infiltration into the brain, thereby reducing CNS inflammation. Our results demonstrate the importance of ZEB1 in microglia-orchestrated neuroinflammation and suggest a potential means for reducing stroke-induced neurological injury.

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Teaser

Li et al. show that ZEB1 overexpression mediates microglia responses and, in turn, inhibits production of astrocytic CXCL1 through the TGF-β1-dependent pathway. Reduced CXCL1 leads to the decline of neutrophil infiltration into the brain. This demonstrates the importance of ZEB1 in microglia-orchestrated neuroinflammation and suggests a potential means for reducing stroke-induced neurological injury.


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