# Purinergic signaling in granuloma-forming Th2 immunity

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $445,021

## Abstract

PROJECT SUMMARY
The type 2 immune response is triggered by intestinal helminth infection and is characterized by elevations in
IL-4, IL-5, IL-13 and other Th2 cytokines. The factors that initiate the type 2 immune response are not yet well
understood and may include release of danger associated molecular patterns, which may be triggered by
tissue damage resulting from intestinal helminths migrating through body tissues. We have recently identified
adenosine, specifically interacting with the A2B adenosine receptor (AR) as a potential danger associated
molecular pattern that may be essential for the development of type 2 immune response to the intestinal
nematode parasite, H. polygyrus. Our studies showed that the intestinal immune response to H. polygyrus is
markedly impaired in A2BAR-/- mice and in wild-type mice given A2BAR antagonists. Our findings further indicate
that mRNA upregulation of the cytokine alarmin, IL-33, is inhibited by A2BAR blockade, raising the possibility
that one mechanism through which A2BAR signaling initiates type 2 immunity is through influencing IL-33
production. In our proposed studies we will examine the role of A2BAR signaling in triggering the release and
subsequent upregulation of IL-33 gene and protein expression. We will further examine specific targets of
A2BAR signaling, including epithelial cells and macrophages, and specifically examine how A2BAR affects the
development of the type 2 primary and memory immune response to H. polygyrus. The mechanisms of
adenosine accumulation, including release and degradation of its precursor ATP will also be studied. These
studies will elucidate the role of adenosine as an endogenous danger signal in the initiation and the
development of the mucosal type 2 immune response and as such will provide significant insights as to how
this important type of immune response may develop.

## Key facts

- **NIH application ID:** 9983656
- **Project number:** 5R01DK113790-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** William Clark Gause
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $445,021
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983656

## Citation

> US National Institutes of Health, RePORTER application 9983656, Purinergic signaling in granuloma-forming Th2 immunity (5R01DK113790-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9983656. Licensed CC0.

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