Maternal NKG2D-mediated immune activation shapes fetal neural development

In women with a history of influenza A virus (IAV) infection, we found an enrichment off CD56dimCD16CD49a natural killer (NK) cells displaying enhanced NKG2D expression in the decidua basalis, as assessed at delivery.

Using IAV- and poly I:C-induced MIA mouse models, we demonstrated that MIA significantly increases the proportion of NK cells at the maternal-fetal interface, characterized by elevated expression of NKG2D, with this local accumulation persisting until late gestation. Importantly, in the poly I:C model, blocking maternal NKG2D through two administrations alleviated prenatal cortical dysplasia, as well as enhancing dendritic plasticity, neural progenitor cells proliferation, and the morphological and transcriptomic changes in cortical excitatory neurons, accompanied by improved ASD-like behaviors in the offspring.