VEGFR-3 deficiency in astrocytes exacerbates the Japanese encephalitis virus infection-induced neuroinflammatory response in the brains of mice

Vascular endothelial growth factor receptor 3 (VEGFR-3), a receptor tyrosine kinase encoded by the FLT4 gene, plays an essential role in regulating the vascular system, especially in the development and maintenance of the lymphatic system.

Although VEGFR-3 expressed in macrophages has been shown to suppress bacterial sepsis and neuroinflammation, its function in astrocytes during JEV infection remains unclear. To investigate this, we generated VEGFR-3 conditional knockout mice with deletion of the ligand-binding domain of VEGFR-3 in astrocytes. VEGFR-3 deficiency in astrocytes led to the upregulated transcription of inflammatory genes and the increased viral load in the brains of JEV-infected mice, ultimately reducing their survival rate.