# Pregnancy influences maternal immune cell function and fetal brain development

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2021 · $627,374

## Abstract

ABSTRACT
Human epidemiological studies suggest that fetuses exposed to maternal inflammation during the late first
or the second trimester have an increased likelihood of neurodevelopmental disorders. Studies are needed
to define the molecular and cellular mechanisms by which immune activation during pregnancy translates into
neurodevelopmental and behavioral abnormalities in children.
Using a mouse model of maternal immune activation (MIA), we demonstrated that Th17 cells are critical
mediators that induce neurodevelopmental disorder-like phenotypes in the affected offspring exposed to
prenatal inflammation. We also demonstrated that inflammation-induced neurodevelopmental disorder
phenotypes in the offspring require maternal intestinal bacteria such as segmented filamentous bacteria (SFB)
that promote Th17 cell differentiation. Moreover, we have spatially and functionally mapped the brain regions
that mediate behavioral abnormalities.
Inflammation during pregnancy in humans, however, does not always lead to the birth of children with
neurodevelopmental disorders, suggesting that there are factors that suppress maternal Th17 cell-dependent,
neurodevelopmental disorder-like phenotypes in the affected offspring. We hypothesize that pregnancy-
associated changes in immune cell function and the composition of commensal bacteria favor anti-
inflammatory responses that dictate both the amplitude and specificity of immune responses against infection
and other inflammatory conditions.
In the proposed application, we will first determine the pregnancy-induced changes in immune cell function and
their impact on MIA-like phenotypes in offspring. Secondly, we will investigate if pregnancy-associated
changes in the bacterial community of the maternal guts contribute to anti-inflammatory responses. Lastly, we
propose that by harnessing pregnancy-associated anti-inflammatory responses we can develop preventive
ways to suppress neuronal and behavioral changes in the MIA-affected offspring.

## Key facts

- **NIH application ID:** 10215459
- **Project number:** 5R01MH119459-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Jun R. Huh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $627,374
- **Award type:** 5
- **Project period:** 2019-09-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215459

## Citation

> US National Institutes of Health, RePORTER application 10215459, Pregnancy influences maternal immune cell function and fetal brain development (5R01MH119459-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10215459. Licensed CC0.

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