# Characterization of innate and IgE-mediated mast cell functions in honeybee venom allergy using Collaborative Cross mice

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $524,610

## Abstract

PROJECT SUMMARY/ABSTRACT
We will use Collaborative Cross (CC) mice to define how genetic traits influence innate and/or IgE-mediated
responses of mast cells (MCs) to honeybee venom. In IgE-dependent allergic reactions, crosslinking of MC
high affinity IgE receptors (i.e., FceRI) by the binding of bivalent or multivalent allergen to antigen-specific IgE
activates MCs to secrete three major classes of products: 1) preformed mediators stored in cytoplasmic
granules, 2) newly synthesized lipid-derived mediators, and 3) cytokines, chemokines and growth factors.
These MC products are responsible for many of the signs and symptoms of allergic diseases. MC activation,
with or without the involvement of IgE, is also thought to contribute to the inflammation, tissue damage, and
even fatal shock induced by envenomation. Components of hymenoptera venoms (e.g., honeybee venom),
pharmaceutical agents, and foods are the most common triggers for anaphylaxis in humans. Many people have
been sensitized to hymenoptera venoms and some unfortunate individuals react after exposure to such insect
stings with serious systemic reactions and even fatal anaphylaxis. However, recent experiments in mice and
zebra fish demonstrate that MC-derived proteases can degrade animal venoms and diminish their toxicity. Also,
IgE/FceRI-mediated MC activation can enhance the survival of mice challenged with honeybee venom or a
snake venom, or with S. aureus bacteria. Yet the benefits of “allergic immune responses”, mediated by IgE/MC-
dependent mechanisms, have not been widely recognized. While the exact mechanisms determining whether
the outcomes of hymenoptera envenomation are detrimental or favorable have been elusive, we know that
genetic factors can significantly influence the development, progression, and severity of allergy and
anaphylaxis. We hypothesize that genetic traits, by modulating the strength and/or composition of MC
responses to honeybee venom and/or the Th2-IgE-MC immune axis, can influence the outcomes of
honeybee stings. In this project, we propose to use genetically diverse CC mice to identify genetic modifiers
regulating MC functions in insect venom allergy. In Aim 1, we will screen a panel of CC mice for their
susceptibility to the toxicity of honeybee venom, development and features of venom-specific type 2 immunity,
and induction of MC activation with or without crosslinking of venom-specific IgE/FceRI. We will also perform
quantitative trait locus (QTL) mapping of the venom-induced phenotypes in CC mice to identify distinct genetic
loci and novel regulators associated with MC-dependent susceptibility vs. resistance to honeybee venom. In
Aim 2, we will confirm, in mouse MCs, important regulators of MC functions that are identified by screening CC
mice using QTL analysis to assess the involvement of these regulators in innate and/or IgE-mediated MC
functions. We think that the identification of genetic modifiers that distinguish beneficial vs. harmful effects of...

## Key facts

- **NIH application ID:** 10681390
- **Project number:** 5R01AI165373-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Stephen Joseph Galli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $524,610
- **Award type:** 5
- **Project period:** 2021-09-22 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10681390

## Citation

> US National Institutes of Health, RePORTER application 10681390, Characterization of innate and IgE-mediated mast cell functions in honeybee venom allergy using Collaborative Cross mice (5R01AI165373-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10681390. Licensed CC0.

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