# Prostaglandin E2-Dependent Control of a Mast Cell IL-33/ST2 Pathway in Asthma

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $859,874

## Abstract

Abstract
This proposal focuses on the potential role of mast cells in the control of type 2 immunopathology (T2I) elicited
by IL-33, a principal effector cytokine involved in the onset and persistence of upper and lower airway
inflammation. Preliminary studies demonstrate that mast cells are required to drive type 2 inflammation when
the levels of prostaglandin E2 (PGE2) are reduced, but paradoxically shift to an anti-inflammatory role when
PGE2 levels are sufficient. We have now found that mast cells are necessary to control the production of
soluble ST2 (sST2), a decoy receptor that binds IL-33 and limits its bioavailability in vivo. Moreover, PGE2
upregulates the expression of sST2 while downregulating the expression of ST2L, the cell surface receptor for
IL-33. Aim 1 will determine the mechanism(s) by which mast cells protect the lung from IL-33-induced T2I, and
identify the mast cell subsets that are responsible. Aim 2 will determine the receptors and molecular
mechanisms by which PGE2 alters the expressions of sST2 and ST2L, and Aim 3 will verify the importance of
these mechanisms in vivo. The studies have strong translational implications for the pathophysiology of
respiratory T2I, and could point the way toward the development of logical therapeutic strategies for asthma
and chronic sinus disease.

## Key facts

- **NIH application ID:** 10817158
- **Project number:** 5R01AI175149-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Joshua A Boyce
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $859,874
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817158

## Citation

> US National Institutes of Health, RePORTER application 10817158, Prostaglandin E2-Dependent Control of a Mast Cell IL-33/ST2 Pathway in Asthma (5R01AI175149-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10817158. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*