# Role of Eosinophils in Hepatic Ischemia Reperfusion Injury

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $386,585

## Abstract

PROJECT SUMMARY
The goal of this proposal is to investigate the functional role of eosinophils during hepatic ischemia and
reperfusion injury (IRI). Hepatic IRI is a significant source of morbidity and mortality during major hepatic
resection and during liver transplantation. Previous studies have shown that following liver transplantation
innate immune cells, such as neutrophils or macrophages, are activated and traffic into the hepatic allograft.
Unexpectedly, we observed that eosinophils also accumulate in the liver following orthotopic liver
transplantation in humans. In contrast, we could not detect any eosinophils in healthy liver biopsies. Similarly,
in a murine model, eosinophils accumulate in the liver in a time-dependent fashion following hepatic IRI.
Functional studies using genetic and antibody-based depletion of eosinophils demonstrate a protective role of
these cells during hepatic IRI. An unbiased screen of gene expression profiles following eosinophil depletion
implicated eosinophil-dependent ST2 in liver protection. Combination of genetic and adoptive transfer studies
suggest that eosinophil-specific IL-33/ST2 signaling attenuates inflammation of the ischemic liver by
dampening hepatic neutrophil accumulation/activation. These findings led to our hypothesis that during
hepatic IRI, eosinophils protect the liver through IL-33/ST2 signaling. Three Specific Aims are proposed
to i) investigate the role of eosinophils and IL-33/ST2 signaling in hepatic IRI, ii) elucidate the mechanism by
which IL-33/ST2 signaling in eosinophils protects against hepatic IRI, and iii) Target IL-33/ST2 signaling in
eosinophils for the treatment of hepatic IRI.

## Key facts

- **NIH application ID:** 9936372
- **Project number:** 5R01DK121330-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Cynthia Ju
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,585
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936372

## Citation

> US National Institutes of Health, RePORTER application 9936372, Role of Eosinophils in Hepatic Ischemia Reperfusion Injury (5R01DK121330-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9936372. Licensed CC0.

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