# Brush cell sensing of aeroallergen-elicited stress signals promotes epithelial cell activation

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $225,203

## Abstract

PROJECT SUMMARY:
Solitary chemosensory cells are rare specialized epithelial cells scattered in the airway (referred to as brush
cells) and intestinal mucosa (named tuft cells), recently found to be initiators of type 2 immune responses at
least partially through the generation of the proinflammatory cytokine IL-25. In the airways, activation of brush
cells by bitter tasting bacterial metabolites also triggers sensory neurons leading to protective airway reflexes.
The full effector potential of chemosensory cells and activating receptors beyond taste receptors have not been
defined.
We have found that epithelial cells sharing the transcriptional profile of chemosensory cells from the trachea
and intestine are enriched in the nasal mucosa. We generated a nasal brush cell RNA-seq data set to
determine their possible activating receptors and developed an ex vivo system to test the ligand receptor pairs
that lead to activation of airway brush cells. We found that brush cells generate large quantities of pro-
inflammatory lipid mediators among them cysteinyl leukotrienes (CysLTs). We then generated a new mouse
strain with genetic deletion of the terminal CysLT generating enzyme in brush cells to define the contribution of
brush cell-derived CysLTs to the pro-inflammatory and protective responses in the airways.
In Aim 1, we will define the subsets of nasal brush cells from the respiratory and olfactory mucosa using single
cell RNA sequencing. In Aim 2, we will define the brush cell activating pathways triggered in response to
aeroallergen sensing, the autocrine loops enhancing this response and the full effector potential of brush cells.
In Aim 3, we will define the role of brush cell-derived CysLTs in epithelial cell activation in the airways using
mice with genetic deletion of brush cells, CysLTs and brush cell-specific deletion of CysLTs. Findings here will
clarify the contribution of brush cell-derived CysLTs to protective and inflammatory responses in the airways
and lay the foundation to define their function in human airway mucosa.
Results from the proposed experiments will provide critical insights into how protective airway responses
designed to expel environmental insults can be diverted to initiate and propagate inflammatory responses
leading to allergic airway diseases.

## Key facts

- **NIH application ID:** 10217812
- **Project number:** 1R21AI154345-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Lora Bankova
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,203
- **Award type:** 1
- **Project period:** 2021-03-02 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217812

## Citation

> US National Institutes of Health, RePORTER application 10217812, Brush cell sensing of aeroallergen-elicited stress signals promotes epithelial cell activation (1R21AI154345-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217812. Licensed CC0.

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