# HISTAMINE-INDEPENDENT MAST CELL NERVE INTERACTIONS IN ALLERGY

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $381,250

## Abstract

Itch is a primary symptom of many allergic conditions, and severely affects the quality of life and
productivity. Primary sensory neurons residing in the trigeminal ganglia and dorsal root ganglia (DRG) play an
essential role in the generation of allergic itch. These neurons detect endogenous itch-inducing molecules
(pruritogens) via a group of itch receptors on their peripheral axons in the skin or mucosal membrane tissues,
and transmit signals to the spinal cord via their central axons. In contrast to the well-studied histamine
pathway, histamine-independent itch pathways in allergic itch remain poorly defined. Previously, we identified
several novel itch receptors within a large family of G-protein‒coupled receptors called Mrgprs. We found that
several Mrgprs recognize distinct pruritogens, and mediate histamine-independent itch. Our latest results
indicate that Mrgprs are required for mast cell-mediated allergic itch. This proposal aims to uncover the
underlying mechanisms. We will test whether Mrgprs mediate the interaction between mast cells and primary
sensory fibers in allergic itch using molecular, genetic and imaging approaches in Aim 1. Furthermore, we will
identify the endogenous Mrgpr ligands released by mast cells upon degranulation in Aim 2. In Aim 3, we seek
to translate our discoveries from mice to humans. Human Mrgprs do not form clear orthologous pairs with
mouse Mrgprs. Their role in itch is therefore unclear. Based on our preliminary data, we hypothesize that
human MrgprX1 mediates neuronal and behavioral response to mast cell-mediated allergy, which will be tested
in Aim 3. These studies will reveal the neural basis underlying allergic itch and will have a significant impact on
both the study of itch pathogenesis and the clinical treatment of itch.

## Key facts

- **NIH application ID:** 9908041
- **Project number:** 5R01AI125743-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Qin Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2016-05-12 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908041

## Citation

> US National Institutes of Health, RePORTER application 9908041, HISTAMINE-INDEPENDENT MAST CELL NERVE INTERACTIONS IN ALLERGY (5R01AI125743-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9908041. Licensed CC0.

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