# The role of peripheral immune cell activity in food-allergy-induced neuroinflammation and demyelination

> **NIH NIH R01** · UNIVERSITY OF NORTH DAKOTA · 2022 · $382,717

## Abstract

PROJECT SUMMARY
Food allergy has been implicated in neuropsychiatric and neurodegenerative disorders. However, the causative
role of food allergy in brain dysfunction has been debated, largely due to insufficient pathological evidence and
clear underlying mechanisms. Using animal models of food allergy, we and others provided supportive evidence
linking food allergy and brain dysfunction by demonstrating that inducing food allergy in otherwise healthy mice
resulted in behavior changes associated with neuroinflammation and altered neural activities. We have found
that C57BL/6J mice sensitized to a bovine whey allergen, β-lactoglobulin (BLG, Bos 5 d), do not exhibit overt
anaphylactic reactions upon acute allergen challenge but showed anxiety-like and depression-like behavior one
day after with elevated plasma levels of allergen-specific IgE and inflammatory cytokines and chemokines. These
observations indicated that allergy-induced immune responses are still present in sensitized individuals even in
the absence of apparent allergic reactions. Taking advantage of this mouse model of non-anaphylactic cow’s
milk allergy (CMA), we subjected BLG-sensitized mice to a repeated allergen exposure regimen by placing them
on a whey-containing diet for 2 weeks to simulate frequent allergen consumption by individuals with subclinical
reactions. Although no evidence of anaphylaxis or food aversion was detected in the allergen-fed mice, we
observed profound cortical demyelination as well as increased blood-brain permeability, perivascular astrocyte
hypertrophy, and immune cell presence in their brains associated with significant depression-like behavior.
Furthermore, the systemic levels of allergen-specific IgE and other inflammatory mediators remained elevated
in these mice. Thus, we hypothesize that CMA-induced cortical demyelination and other neuropathologies result
from neuroinflammation orchestrated by sustained activities of brain-infiltrating leukocytes due to repeated
allergen exposure. In this project, we will first assess whether sensory, motor, and/or cognitive functions are also
affected by the CMA-associated demyelination and neuroinflammatory changes in the brain and whether
removing the allergen from the diet reverses the changes in the brain and behavior (Aim 1). We will then
investigate the involvement of allergen-stimulated immune cells in the development of neuropathologies by
clarifying their role in mediating the peripheral allergic insult to the brain (Aim 2). Finally, we will test whether
pharmacological protection of the intestinal barrier prevents aberrant allergen entry during food consumption and
reduces CMA-induced neuropathologies (Aim 3). The outcomes of this study will fill our knowledge gaps in the
mechanism involved in peripheral-to-central communication and clarify the adverse effects of allergy-mediated
chronic inflammation on brain function, prompting early allergy detection to prevent brain dysfunction.

## Key facts

- **NIH application ID:** 10412267
- **Project number:** 1R01AI168563-01
- **Recipient organization:** UNIVERSITY OF NORTH DAKOTA
- **Principal Investigator:** Kumi Nagamoto-Combs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,717
- **Award type:** 1
- **Project period:** 2022-04-18 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412267

## Citation

> US National Institutes of Health, RePORTER application 10412267, The role of peripheral immune cell activity in food-allergy-induced neuroinflammation and demyelination (1R01AI168563-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10412267. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*