NK cells in neurodevelopment.

Maternal immune activation (MIA) during pregnancy perturbs fetal neurodevelopment, with natural killer (NK) cells emerging as key contributors to neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD).

Clinical studies consistently report NK cell dysfunction in ASD patients and their mothers, characterized by altered cytotoxicity, hyperactivation at rest, functional exhaustion on stimulation, and skewed receptor/genetic profiles.

Uterine NK (uNK) cells, indispensable for placental and fetal development, can paradoxically promote NDDs when hyperactivated, releasing granzyme B (GZMB) that disrupts fetal brain structure and function.

Elucidating the MIA-driven ‘uNK/ GZMB–microglia–NDD’ axis is essential to devise preventive strategies for high-risk pregnancies and identify early biomarkers of neurodevelopmental risk. sciencenewshighlights ScienceMission https://www.cell.com/cms/10.1016/j.it.2025.10.001/asset/89cd…ts/gr3.jpg https://sciencemission.com/Janus-face-of-NK-cells

Maternal immune activation (MIA), triggered by infection or inflammation during pregnancy, is a well-recognized risk factor for neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). Clinical cohort studies and rodent models suggest that natural killer (NK) cells play a significant role in NDD pathogenesis, but the underlying mechanisms remain poorly defined. Here, we summarize the key immune mediators involved in MIA-induced NDDs, emphasizing microglia as a central hub. We then examine emerging evidence implicating aberrant NK cell activation in ASD, underscoring their overlooked contribution to impaired neurodevelopment. Finally, we discuss potential mechanisms of NK cell–microglia crosstalk in NDDs. Elucidating these interactions in the context of MIA will be crucial for developing preventive and therapeutic strategies against inflammation-driven NDDs.