# Investigating the role of IgE independent mast cell responses in allergic sensitization

> **NIH NIH F30** · YALE UNIVERSITY · 2020 · $30,330

## Abstract

7. Project Summary/Abstract
 Allergy is a disorder of the immune system that occurs following sensitization to an allergen. Allergic
sensitization results in immunological memory against an allergen that enables the body to quickly respond to
subsequent allergen challenges. In the allergic response, mast cell activation causes several allergic
symptoms via degranulation of pre-formed inflammatory mediators. This process can occur through
immunoglobulin E (IgE)-dependent or -independent pathways. IgE-dependent mast cell activation is classically
appreciated for its role in the allergic response after allergic memory has developed; however, the
physiological relevance of IgE-independent mast cell responses is less understood. The MAS-related G
protein-coupled receptor B2 (MRGPRB2) is a mast cell-specific receptor that induces mast cell activation upon
binding small cationic molecules such as compound 48/80. While MRGPRB2 has been implicated in pseudo-
allergic drug reactions, the immunological consequences of MRGPRB2-mediated mast cell activation are
incompletely characterized. The objective of this proposal is to study the role of IgE-independent mast cell
responses in the context of allergic sensitization. Based on preliminary data that compound 48/80 induces
allergic memory in a mouse model of allergic airway inflammation, we hypothesize that allergic sensitization
requires MRGPRB2-mediated mast cell activation. To test this hypothesis, two aims will be investigated. The
first aim will examine the dependence of 48/80-mediated allergic sensitization on mast cells and on MRGPRB2
using mice that are deficient in mast cells or MRGPRB2. The second aim will investigate the downstream
effect and dependence of 48/80-mediated allergic sensitization on dendritic cells using CD11c-deficient, mast
cell-deficient, and MRGPRB2-deficient mice. Together, these studies will provide insight into mast cell function
and may identify a previously uncharacterized role of mast cells in allergic inflammation. Alongside this
research, the applicant will complete a program of advanced coursework, clinical electives, and scientific skill
building under the close mentorship of her advisor. The research and training detailed in this application will
prepare her to pursue a clinically relevant basic science career as an independent physician-scientist.

## Key facts

- **NIH application ID:** 10054649
- **Project number:** 5F30AI145102-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Alyssa Mitson-Salazar
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,330
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054649

## Citation

> US National Institutes of Health, RePORTER application 10054649, Investigating the role of IgE independent mast cell responses in allergic sensitization (5F30AI145102-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10054649. Licensed CC0.

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