# Cellular and molecular mechanisms of mucosal organ crosstalk in allergic diseases

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $470,319

## Abstract

Abstract
Allergic diseases including food allergies and allergic asthma represent a substantial health and economic
burden, with the US Centers for Disease Control (CDC) estimating more than 50 million people within the US
suffering from some form of allergic disease. The natural history of allergic diseases suggests immunological
crosstalk between mucosal organs contributes to the co-occurrences of allergic diseases (e.g. food allergy and
asthma) within the same individual, although the cellular and molecular mechanisms that underly this process
have not been defined and represent a critical knowledge gap. Using in vivo mouse models we have shown
that intragastric administration of allergen (ovalbumin, OVA) to OVA-sensitized mice not only elicits local
eosinophilic inflammation within the allergen-exposed intestine, but also increases the frequency and alters the
activation phenotype of tissue eosinophils within the allergen non-challenged, remote lung. Presence of
inflammatory eosinophils within the remote lung are associated with mucous metaplasia and airway priming;
the latter evidenced by generation of an exacerbated allergic airway inflammatory response upon subsequent
inhalation of sub-optimal doses of an unrelated antigen (house dust mite). In contrast, intragastric OVA failed
to enhance mucous metaplasia or airway priming in the remote lungs of eosinophil deficient mice. Collectively
these prior data suggest intragastric challenge affects allergic susceptibility of the airways through
dysregulation of lung tissue eosinophils. This proposal builds on these findings to investigate lung- and
eosinophil-intrinsic mechanisms that underly intragastric allergen-driven dysregulation of remote lung
eosinophils that lead to remote airway priming. We have found intragastric allergen challenge transiently alters
the lung transcriptome, including induction of gene signatures implicated in eosinophil recruitment. Correlative
analyses of serum proteins and blood eosinophil-expressed receptors further suggest systemic mediators and
eosinophil-intrinsic factors contribute specifically to lung homing, including an eosinophil-derived subset of
extracellular vesicles (EVs). Specific Aims test the central hypothesis: Intragastric allergen challenge
activates 1) an IL-13:CCL11 axis in the remote lung via gut-derived type 2 innate lymphoid cells
(ILC2s), and 2) IL-5/IL-33:ST2-dependent effects on circulating eosinophils that synergistically underly
the dysregulation of tissue eosinophils within the remote lung. Our approach utilizes unique genetically
modified mouse strains, including cytokine reporter mice and cell-targeted gene disruption, competitive
adoptive transfer studies and innovative approaches to characterize eosinophil-derived extracellular vesicles.
Translational approaches utilize human blood eosinophils. Completion of this proposal may offer important
insights into immunological mechanisms that drive mucosal remote organ priming within the conte...

## Key facts

- **NIH application ID:** 10418019
- **Project number:** 1R01AI168134-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Lisa Ann Spencer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $470,319
- **Award type:** 1
- **Project period:** 2022-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418019

## Citation

> US National Institutes of Health, RePORTER application 10418019, Cellular and molecular mechanisms of mucosal organ crosstalk in allergic diseases (1R01AI168134-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10418019. Licensed CC0.

---

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