# CysLT and P2Y Receptors in Lung Inflammation

> **NIH NIH R37** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $535,507

## Abstract

This proposal for extended support is focused on the mechanisms and cell types by which the
purinergic type 6 (P2Y6) receptor regulates the magnitude of allergen-induced type 2 immunity in
the respiratory tract. P2Y6 receptor deletion sharply enhances pulmonary eosinophilic inflammation
and type 2 cytokine generation in models of asthma induced by allergens from both the dust mite
Dermatophagoides farinea and the mold Alternaria alternata. During the current period of support,
we developed mice selectively lacking P2Y6 receptors on dendritic cells (DCs). Surprisingly, studies
using these mice indicate that DC-associated P2Y6 receptors contribute only modestly to the
protective effects observed in the global knockouts. Furthermore, our more recent studies suggest
prominent expression of P2Y6 receptors by epithelial progenitor cells in the airways of patients with
severe asthma. The studies going forward will use a combination of approaches in transgenic mice
and human cells and samples to test the hypothesis that P2Y6 receptor signaling in epithelial
progenitors controls type 2 immune responses through regulating cytokine secretion, epithelial
repair, and tuft cell development. The studies should provide valuable information on the processes
that regulate homeostasis in type 2 immunity that modifies the risk and severity of asthma.
RELEVANCE (See instructions):
This proposal seeks to understand how a molecule known as the P2Y6 receptor contrils the
severity of inflammation in asthma. The studies should reveal potential factors that contribute to
asthma severity and could lead to new therapies.

## Key facts

- **NIH application ID:** 9833482
- **Project number:** 5R37AI052353-18
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Joshua A Boyce
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $535,507
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9833482

## Citation

> US National Institutes of Health, RePORTER application 9833482, CysLT and P2Y Receptors in Lung Inflammation (5R37AI052353-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9833482. Licensed CC0.

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