# Prenatal control of offspring airway responsiveness

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $590,493

## Abstract

We have recently shown that there is a fundamental difference in airway physiology between wildtype mice
born to wildtype mothers and wildtype mice born to IL5 overexpressing mothers or housedust mite (HDM)
sensitized mothers. The airways of adult wildtype offspring of these mothers are much more responsive, an
effect that requires fetal eosinophilia that develops as the result of maternal IL5 crossing the placenta.
Subsequent sensitization and challenge with housedust mite yields much more severe bronchoconstriction.
 The central hypothesis of this project is that high circulating IL5 during pregnancy induces fetal
eosinophilia, and that this causes permanent changes in airway innervation that increase
bronchoconstriction. In this project, we propose to determine the mechanisms of airway hyperreactivity in
these WT offspring of IL5 transgenic mothers. We will characterize changes in airway nerve structure,
transmitters, and receptor expression. We propose three specific aims:
SPECIFIC AIM #1: Test the effects of maternal IL5tg and maternal HDM challenge on reflex
bronchoconstriction, parasympathetic nerve function, and smooth muscle function. We will determine the
role of maternal fetal transfer of IL5 in the maternal HDM challenge model, and test the role of maternal and
fetal eosinophilia in these effects. We will also dissect the mechanisms of severe, lethal bronchoconstriction
and potentiated airway inflammation when these adult offspring are antigen challenged.
SPECIFIC AIM #2: Test whether exposure to IL5 in utero alters the architecture or neurotransmitter content
of sensory and parasympathetic nerves. We will use our novel imaging method to determine epithelial and
smooth muscle innervation, and to quantify changes in neurotransmitter expression in sensory and
parasympathetic nerves.
SPECIFIC AIM #3: To determine the role of airway epithelial neurotrophins in 1) heightened response to
antigen challenge, 2) severe airway hyperresponsiveness, and 3) maintenance of airway nerve remodeling in
adult offspring of IL5tg mothers and in adult offspring of HDM sensitized and challenged mothers. We will
extend our preliminary studies of neurotrophin expression to include the different mouse models and
treatments in Aim #1, and determine the roles of neurotrophins that are elevated by blocking with antibodies
and treating animals with receptor antagonists.

## Key facts

- **NIH application ID:** 10122985
- **Project number:** 5R01HL144008-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** David B Jacoby
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $590,493
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122985

## Citation

> US National Institutes of Health, RePORTER application 10122985, Prenatal control of offspring airway responsiveness (5R01HL144008-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10122985. Licensed CC0.

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