Maternal NKG2D-mediated immune activation shapes fetal neural development

Area of Science:

• Immunology
• Neuroscience
• Developmental Biology

Background:

• Maternal immune activation (MIA) disrupts immune homeostasis at the maternal-fetal interface, potentially causing developmental abnormalities like autism spectrum disorder (ASD).
• Specific natural killer (NK) cell populations with enhanced NKG2D expression are found in the decidua of women with a history of influenza A virus (IAV) infection.

Purpose of the Study:

• To investigate the role of NK cells and NKG2D in MIA-induced neurodevelopmental disorders.
• To evaluate the therapeutic potential of blocking NKG2D in mitigating MIA-associated neurodevelopmental deficits.

Main Methods:

• Utilized mouse models of MIA induced by IAV and poly I:C.
• Analyzed NK cell populations and NKG2D expression at the maternal-fetal interface.
• Administered NKG2D blockade and assessed neurodevelopmental outcomes, including cortical structure, neuronal plasticity, and behavior.

Main Results:

• MIA increased NK cell accumulation and NKG2D expression at the maternal-fetal interface in mice.
• Dual administration of maternal NKG2D blockade in the poly I:C model alleviated cortical dysplasia, enhanced neuronal development, and improved ASD-like behaviors.
• NKG2D blockade altered neurodevelopment-related gene expression in excitatory neurons.

Conclusions:

• NK cell modulation via NKG2D blockade presents a potential therapeutic strategy for neurodevelopmental disorders associated with maternal infection.
• Targeting NKG2D may offer a way to counteract the detrimental effects of MIA on fetal neurodevelopment.