# Project 1: Immune development and respiratory outcomes in children from diverse Wisconsin communities

> **NIH NIH U19** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $1,080,106

## Abstract

PROJECT SUMMARY
The early life immune system requires “training” to decrease vulnerability to infectious diseases and is the time
period when risks for development of non-communicable, immune-mediated diseases, such as allergic diseases,
are established. Early life exposure to the farming environment has been shown to provide a protective role
against the development of allergic diseases. We have successfully established a novel birth cohort called
Wisconsin Infant Study Cohort (WISC). WISC is a rural US birth cohort with infants from dairy farms, rural, non-
farming environments, and infants from Amish communities who have a very Traditional Agrarian (TA) lifestyle.
Our study findings demonstrate decreased incidence of atopic dermatitis, decreased viral respiratory illness
frequency and increased LPS-induced monocyte cytokine production during the first year of life in farm-exposed
infants. Our preliminary data demonstrate TA children have very low rates of allergic disease, unique gut and
nasal microbiota, and increased innate maturation and immune regulatory markers compared to farm and non-
farm children through age 2 years. There remain unresolved and important questions as to whether and how
innate immune cell competence and immunoregulatory function are related in early life and their risk for disease.
A major goal of this proposal is to define the immune and environmental signatures for protection from allergic
and viral respiratory diseases in farm exposed children and determine the relationship between immune, nasal
epithelial profiles and microbiome. Our central hypothesis is that farm-related microbial colonization
promotes the development of distinct immune and nasal epithelial phenotypes mediated, in part, through
epigenetic changes that reduce risk for allergic sensitization and increase mucosal antiviral responses.
We hypothesize the Amish will have distinct immune profiles and microbial exposures, the farm participants will
be intermediaries, and non-farm considered a relatively at-risk study group. To address this hypothesis, we will
continue WISC+ through age 5 years and establish a new cross-sectional cohort. Our study consists of three
aims and makes use of cutting-edge technologies that leverages our extensive experience with farm-related birth
cohorts and study team expertise. Aim 1. To characterize the longitudinal phenotypes and epigenetic trajectory
of monocyte and regulatory immune cells of the TA, farm and non-farm children through age 5 years. Aim 2. To
determine the relationship between TA and farm exposures, nasal airway epithelial cell gene expression and
response to naturally occurring viral respiratory illness. We will conduct an observational, cross-sectional, case-
control cohort study (called Microbial Associated Respiratory Illnesses, MARI) of three groups of school-age
children (100/group): TA children, suburban children without asthma, and suburban children with asthma to
examine nasal mucosal physiology, a...

## Key facts

- **NIH application ID:** 10813827
- **Project number:** 5U19AI104317-12
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** CHRISTINE Marie SEROOGY
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,080,106
- **Award type:** 5
- **Project period:** 2013-02-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813827

## Citation

> US National Institutes of Health, RePORTER application 10813827, Project 1: Immune development and respiratory outcomes in children from diverse Wisconsin communities (5U19AI104317-12). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10813827. Licensed CC0.

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