# Allergen-elicited signaling cascades in olfactory microvillous tuft cells

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $260,600

## Abstract

PROJECT SUMMARY:
The nasal mucosa consists of two distinct compartments - olfactory neuroepithelium and respiratory
epithelium. As such, the nose serves as both a respiratory and as a sensory organ. Among the epithelial cells
strategically positioned at the apical surface at the site of interaction with the inhaled air in the olfactory and
respiratory epithelium are two populations of specialized cells with shared core mediator profile but distinct
receptor repertoire – the olfactory TRPM5+ microvillous cells (MVCs) and the respiratory solitary chemosensory
cells (SCCs). While bitter taste receptors, bitter tasting bacterial metabolites and succinate are well defined
ligands of respiratory tuft cells (tracheal brush and respiratory SCCs), the ligands and signaling pathways of
olfactory TRPM5+ MVCs are less well defined. We recently found that TRPM5+ MVCs detect allergens and the
danger signal ATP to generate proinflammatory mediators including cysteinyl leukotrienes and prostaglandins
in an in vitro system. We also demonstrated that allergen recognition by the olfactory TRPM5+ MVCs initiates
an aberrant response of stem cell proliferation in the absence of profound inflammation in the olfactory
mucosa. Here, we will determine how the TRPM5+ MVCs contribute to the integrated airway epithelial
response to allergens and the determinants of pro- vs anti-inflammatory programs directed by these new
members of the tuft cell family.
 In Aim 1, we will define the signaling components engaged upon allergen detection by TRPM5+ MVCs. In
Aim 2, we will determine how signals detected by TRPM5+ MVCs are propagated in the olfactory
neuroepithelium, and the mediators (eicosanoids, epithelial cytokines, acetylcholine) generated by TRPM5+
MVCs or immediately downstream of them.
 Findings here will clarify how the olfactory TRPM5+ MVC tuft cells detect allergens, the consequences of
their activation, and possible therapeutic targets.

## Key facts

- **NIH application ID:** 10948815
- **Project number:** 1R21AI185057-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Lora Bankova
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $260,600
- **Award type:** 1
- **Project period:** 2024-06-03 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10948815

## Citation

> US National Institutes of Health, RePORTER application 10948815, Allergen-elicited signaling cascades in olfactory microvillous tuft cells (1R21AI185057-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10948815. Licensed CC0.

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