Cerebroid Study Connects IL-17A Exposure With Altered Human Fetal Cortex Development

Researchers at the University of Aberdeen used a three-dimensional model of developing human brain tissue to investigate how an inflammatory signal associated with maternal immune activation might affect the fetal cerebral cortex. The study, published in Nature Neuroscience, reported that exposure to IL-17A altered several features of early cortical development in the laboratory model.

The model, called a cerebroid, consisted of small pieces of human fetal brain tissue maintained outside the body in a controlled, nutrient-rich environment. The tissue came from the dorsolateral prefrontal cortex and was collected following elective pregnancy termination. Unlike organoids, which are grown from stem cells and simplify the structure of an organ, cerebroids retain much of the cellular diversity, organization, and architecture of developing human cortical tissue, according to the report.

The researchers exposed the cerebroids to IL-17A, an inflammatory signaling protein linked with maternal immune activation. They then examined tissue thickness and folding, along with the production and maturation of neurons. Microscopy and cell-labeling methods were combined with RNA sequencing and proteomics to investigate structural and molecular changes.

The team reported that IL-17A exposure caused the developing cortex to fold prematurely. It was also associated with increased cortical thickness and accelerated neuron production and maturation. The researchers found evidence that IL-17A acted directly on neural stem cells and identified sustained activation of the NF-κB signaling pathway as an important mechanism associated with the observed changes.

When the researchers blocked that pathway, many of the effects were reversed in the cerebroid model. That result points to a biological process for further investigation, but it does not establish that blocking NF-κB would produce the same outcome in a pregnancy or in a developing human brain.

The findings also do not demonstrate that maternal inflammation causes neurodevelopmental conditions. Instead, they provide laboratory evidence about how one inflammatory signal may influence early human cortical tissue. The work used ex vivo fetal brain tissue rather than a clinical study of pregnant people or fetuses, so its findings cannot by themselves establish effects on brain development in humans in the womb.

The researchers plan to examine how additional developing brain cell types, including the brain’s immune cells, blood vessels, and specialized neural stem cells, respond to inflammatory signals. They also intend to create cerebroid models from other brain regions to determine whether those areas respond differently. The study was led by Muhammad Z. K. Assir and colleagues and reported in the 2026 issue of Nature Neuroscience.