# Project 3: Physical neuro-immune interactions during food allergy

> **NIH NIH P01** · FOOD ALLERGY SCIENCE INITIATIVE, INC. · 2024 · $593,250

## Abstract

ABSTRACT
The GI tract hosts as many neurons (enteric-associated neurons, EANs) as the spinal cord and more immune
cells than all other compartments together. Bidirectional interactions between immune and neuronal cells have
been documented during steady state and are proposed to be part of several disease processes, ranging from
multiple sclerosis to irritable bowel syndrome (IBS), and food allergy. With complementary expertise using
orthogonal approaches, our individual groups within this program and collaboration between our labs have
substantially contributed to the neuroimmune field by uncovering sensing mechanisms from the immune and
nervous systems that monitor perturbations at the luminal surface. In Project 3, we will investigate whether
physical interactions between enteric neurons, immune cells, and enteroendocrine cells (EEC) play major roles
in sensitization to food antigen (sensitization phase) or during allergic response (effector phase), dictating the
severity of food allergy. The experiments proposed here will complement Project 1 by defining cellular partners
in the gut epithelium, including EEC-neurons and EEC-immune cells, at different phases of allergic responses.
Project 3 will also complement studies performed by the Liberles lab in Project 2 by defining functional changes
in local enteric neurons and epithelial cells contacting vagal sensory neurons. In Aim 1, we will define
transcriptional changes in enteric neurons following allergic sensitization in mice (with Bioinformatics Core). We
will also characterize morphological or structural changes in enteric neurons during allergic responses utilizing
3D-tissue clearing imaging tools (interface with Project 1). In Aims 2&3, we will take advantage of uLIPSTIC,
recently developed in collaboration with G. Victora (Rockefeller). This new mouse genetic approach allows for
contact-dependent labeling of cell-cell interactions in specific cell types. To identify epithelial-neuron-immune
partners, we will use neuronal uLIPSTIC, allowing in vivo labeling of non-neuronal cells via neuronal-restricted
sortase expression upon cell-cell contact. Using a combination of imaging and gene-reporter mouse strains, we
will define whether neuron-immune cell interactions change spatially under allergic versus non-allergic
conditions. Finally, we will use genetically engineered mouse strains and AAV constructs using our Transgenic
Core to target or modulate specific immune or neuronal pathways in the context of allergic sensitization (interface
with Projects 1 and 2). In Aim 3, we will identify EEC-interacting partners during physiology, allergic sensitization
and effector phases, in collaboration with the Liberles lab. We will use mouse strains restricting LIPSTIC sortase
expression to EECs in the small and large intestine. With the Bioinformatics and Transgenic Cores, we will
transcriptionally profile FACS-sorted LIPSTIC labelled and unlabeled cells during steady state or food allergy,
characteriz...

## Key facts

- **NIH application ID:** 10762664
- **Project number:** 1P01AI179273-01
- **Recipient organization:** FOOD ALLERGY SCIENCE INITIATIVE, INC.
- **Principal Investigator:** Daniel S Mucida
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $593,250
- **Award type:** 1
- **Project period:** 2024-05-14 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10762664

## Citation

> US National Institutes of Health, RePORTER application 10762664, Project 3: Physical neuro-immune interactions during food allergy (1P01AI179273-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10762664. Licensed CC0.

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