# Neuroimmune interactions regulate development of allergic inflammation

> **NIH NIH R37** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $602,800

## Abstract

PROJECT SUMMARY
 Atopy, Asthma and food allergies are highly prevalent inflammatory disorders that are increasing at an epidemic
 rate. Progression of allergies from one system to other, ultimately involving multiple organs, called “atopic march” is
 not uncommon in infancy. Aberrant type 2 immune responses to allergens have long been appreciated as the
 major driver of allergic reactions, with symptoms of very severe bronchospasms in asthma to vomiting and diarrhea
 observed in food allergies. Type II cytokines (IL-4 and IL-13) are both the drivers and effector molecules that drive
 allergic reactions. It is believed that IL-4 and IL-13 cytokines work on innate and adaptive immune system to induce
 and perpetuate type II inflammatory allergic reactions. We undertook a scRNAseq analysis to identify the cell types
 where IL-13R is expressed and we identified a cluster of enteric sensory neurons and multiple clusters of DRG and
 nodose ganglion neurons that express IL-13-specific receptors. This raises the issue of what is the role of IL-13R on
 the sensory neurons in the lung and gut in regulating allergic inflammation. Our preliminary data show that enteric
 neuron-specific deletion of IL-13R (Il13ra1) failed to control the worm burden and fecundity of the intestinal helminth
parasite Heligmosomoides Polygyrus (Hp). Furthermore, Hp-infected Il13ra1 conditional knock-out (cKO) mice
 displayed severe impairments in the upregulation of Nmu and Calcb neuropeptide expression, suggesting neuronal
 IL-4/IL-13-receptor signaling contributes to the amplification of immunomodulatory neuropeptide expression during
 intestinal helminth infection. Initial scRNAseq of the immune and non-immune cells of the intestines of the Hp-
 infected IL-13R conditional knock-out mice suggest epithelial cell reprogramming and reduction is the number of
ILC2. Based on these preliminary data, we hypothesize that cytokine-neuropeptide feedback loops between
 immune cells and neurons regulate type 2 inflammation and the development of type II allergic inflammation. We
 propose two specific aims to address this hypothesis:
 1) Determine the role of type -2 cytokine receptor, specifically IL-13R signaling in neurons for the
 development of type 2 inflammation in the lung and gut; 2) How do the cytokine receptors on
 enteric neurons affect barrier integrity and host defense?
Together these two aims will begin to address the functional role of type II cytokine receptors (specifically
IL-13R) in regulating neuronal activation, neuropeptide production, and development of type II inflammation.
The project will also focus on characterizing novel molecular interactions between cytokines, neurons and the
immune system to regulate the differentiation and function of the innate and adaptive immune system, with an
ultimate aim to find translatable therapeutic targets for chronic allergic diseases.

## Key facts

- **NIH application ID:** 10801741
- **Project number:** 2R37AI139536-06
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** VIJAY K. KUCHROO
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $602,800
- **Award type:** 2
- **Project period:** 2023-11-28 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801741

## Citation

> US National Institutes of Health, RePORTER application 10801741, Neuroimmune interactions regulate development of allergic inflammation (2R37AI139536-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10801741. Licensed CC0.

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