An immune cell may explain how maternal inflammation causes neurodevelopmental disorder

A research group led by Nagoya University Graduate School of Medicine in Japan has uncovered a potential mechanism linking maternal inflammation to delayed neurodevelopment in infants. The research suggests the role of CD11c-positive microglia—immune cells in the brain crucial for myelination—during infant brain development. The results, published in Communications Biology, suggest new strategies to mitigate the long-term neurodevelopmental effects of maternal inflammation.

Inflammation during pregnancy occurs when the mother’s immune system becomes activated during pregnancy, typically due to an infection, autoimmune response, or environmental factors. It can have negative outcomes for the baby, potentially causing long-term cognitive and behavioral challenges.

Now, a research team led by Kazuya Fuma and Tomomi Kotani has discovered the role of CD11c-positive microglia in this process. Microglia, the brain’s immune cells, play a key role in myelination, the process where nerve fibers are coated with myelin. Myelin is essential for making the nerve cells able to transmit electrical signals efficiently.

First, the researchers tested mice that were exposed to maternal inflammation. They found that the proliferation of these cells was reduced. Then, to determine if these findings were relevant to humans, the researchers analyzed cord blood from preterm infants exposed to chorioamnionitis, a condition that causes inflammation during pregnancy. They found lower levels of IGF-1, a protein linked to CD11c-positive microglia, in their samples. When they performed MRI of the infants, the scans confirmed that they had a higher incidence of delayed myelination.

“Inflammation during pregnancy suppressed the increase in CD11c microglia that we usually see during typical infant development,” Fuma said. “CD11c microglia have been reported to be involved in myelination by being a major source of IGF-1. In the present study, both were decreased in inflammation during pregnancy, suggesting that this pathway is impaired in children with delayed neurodevelopment.”

This study sheds light on the complex relationship between maternal inflammation and neurodevelopment. The researchers hope that understanding the role of CD11c-positive microglia in neurodevelopment will lead to new therapeutic strategies.

“If future studies confirm a decrease in these microglia in preterm infants exposed to inflammatory conditions, such as chorioamnionitis, early interventions could be developed to prevent or reduce the neurodevelopmental impact of maternal inflammation,” Fuma said. “By targeting CD11c-positive microglia, it may be possible to protect infants from the long-term consequences of impaired myelination and improve their chances for healthy cognitive development.”

The study, “Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders,” was published in Communications Biology on January 17, 2025, at DOI: 10.1038/s42003-025-07511-3.

Authors:

Kazuya Fuma, Yukako Iitani, Kenji Imai, Takafumi Ushida, Sho Tano, Kosuke Yoshida, Akira Yokoi, Rika Miki, Hiroyuki Kidokoro, Yoshiaki Sato, Yuichiro Hara, Tomoo Ogi, Kohei Nomaki, Makoto Tsuda, Okiru Komine, Koji Yamanaka, Hiroaki Kajiyama, Tomomi Kotani

Media Contact:

Matthew Coslett

International Communications Office, Nagoya University

Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image: In neonatal mice exposed to maternal inflammation, the proportion of CD11c-positive microglia (yellow) was reduced compared to control mice. Microglia are shown in red, and CD11c-positive cells in green. Scale bar = 100 µm. (credit: Kohei Nomaki)