Modeling Prenatal Immune Activation in Human Brain Organoids Uncovers IL-6-Dependent Interneuron Dysmaturation

Prenatal inflammation has been associated with an increased likelihood of the child developing neurodevelopmental conditions, such as autism spectrum disorder (ASD). Several pro-inflammatory cytokines are significantly upregulated and play critical roles during immune activation, with interleukin-6 (IL-6) being particularly prominent. However, the specific impact of elevated IL-6 levels on human neural development remains to be elucidated. To address this, we established a human pluripotent stem cell-based forebrain organoid model enriched for multiple interneuron lineages, validated through immunohistochemistry and transcriptomic alignment with human fetal reference datasets. We showed IL-6