# Lipid Regulation of the Development of Responsiveness to Allergen in Neonates and Infants

> **NIH NIH U01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $468,666

## Abstract

In animals and humans, offspring of allergic mothers have increased responsiveness to allergen. The maternal
mediators of allergic mothers that increase allergen responsiveness in the offspring are not known. We
demonstrated that the fetal liver and offspring of allergic mice have increased numbers of distinct DC subsets.
Transfer of splenic dendritic cells (DCs) from neonates of allergic mothers to recipient neonates from non-
allergic mothers transfers allergic responsiveness to the recipient neonates. We propose the NOVEL
CONCEPT that immunoregulatory lipids in allergic mothers are transported to the offspring and that altered
levels of these lipids in the offspring of allergic mothers mediate enhancement of offspring responsiveness to
allergens. The following is the rationale for this novel concept: During allergic inflammation in humans and
mice, lipid metabolites are altered. Maternal lipids can then across the placenta to the fetus or are in the
mother's milk during nursing. Lipid metabolites regulate DC differentiation and function, and DCs mediate
initiation of allergic disease. In addition, because we demonstrated that maternal supplementation with α-
tocopherol (α-T) reduces or γ-tocopherol (γ-T) elevates allergic inflammation in offspring, we propose that early
in life, consumption of α-T and γ-T modulate endogenous lipid metabolites in allergic mothers that then
regulate the development of offspring DC subsets that are critical for allergies in offspring. Consistent with our
novel concept, our preliminary data demonstrate an increase in pro-inflammatory lipids and a decrease an anti-
inflammatory lipids in the plasma and placentas of allergic mothers on mouse gestational day 18 (GD18). The
decrease in anti-inflammatory lipid metabolites was blocked by maternal diet supplementation α-T. Thus, our
central HYPOTHESIS is that maternal lipid metabolites elevate numbers of DCs in the fetus and neonate and
that α-T reduces and γ-T elevates lipid metabolites that regulate 1) allergic responses and 2) DC subsets
during the initiation of allergic lung responses. Aim 1. Test the hypothesis that, in allergic mothers, there are
changes in pro-inflammatory lipid metabolites and anti-inflammatory lipid metabolites that can be transferred
across the placenta to the fetus and in the milk to neonates. We will also determine whether the exogenous
supplementation with α-T inhibits and γ-T elevates the generation of the endogenous lipid metabolites. Aim 2.
Test the hypothesis that altered pro-inflammatory and anti-inflammatory lipid metabolites in allergic mothers
regulate offspring development of DCs and allergic inflammation. It will also be determined whether human
cord blood plasma lipid metabolites associate with infant atopy, DC numbers and DC function. Aim 3. Test the
hypothesis that the lipid metabolites, which are altered in allergic mothers, regulate DCs in vitro. Successful
completion of these studies will have a significant impact on 1) our u...

## Key facts

- **NIH application ID:** 10143179
- **Project number:** 5U01AI131337-06
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** JOAN M COOK-MILLS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $468,666
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143179

## Citation

> US National Institutes of Health, RePORTER application 10143179, Lipid Regulation of the Development of Responsiveness to Allergen in Neonates and Infants (5U01AI131337-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10143179. Licensed CC0.

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