IL-17A Exposure in Human Cerebroids Triggers Premature Cortical Folding via NF-κB
Cerebroid experiments establish that IL-17A directly alters human cortical development through NF-κB, providing a mechanistic bridge between maternal inflammation and offspring neurodevelopmental risk. The work highlights opportunities for targeted immunomodulation during pregnancy while underscoring the limits of current ex-vivo models.
This ex-vivo model cannot capture systemic maternal-placental feedback or postnatal experience-dependent refinement; replication in non-human primate pregnancies with timed IL-17A infusion and longitudinal behavioral phenotyping is required before clinical translation. Evidence quality is moderate: controlled interventional design on primary human tissue demonstrates mechanism but lacks in-vivo dosing kinetics and long-term circuit outcomes. Next studies must test whether selective NF-κB or IL-17 receptor antagonists given to the dam prevent the folding phenotype and later neurodevelopmental deficits.
Berg et al.: Timed IL-17A infusion in pregnant macaques will produce measurable cortical folding on fetal MRI by gestational day 120 in at least 70% of exposed animals versus <10% controls by end of 2027.
Sources (2)
- [1]Primary Source(https://www.nature.com/articles/s41593-025-02015-3)
- [2]Supporting Source(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01234-5/fulltext)