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.
https://www.cell.com/trends/immunology/fulltext/S1471-4906(25)00245-5
