# The Role of Eosinophils in the Lung Allograft

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $512,800

## Abstract

PROJECT SUMMARY/ ABSTRACT
It has become accepted canonical dogma that granulocytes, such as eosinophils, play a deleterious and
uniformly destructive role in lung allograft survival. In direct contrast to this notion our laboratory has made the
surprising observation that eosinophils are essential for lung allograft tolerance. Specifically, we demonstrate
that in the presence of co-stimulatory blockade immunosuppression the lung allograft is rapidly infiltrated by a
high numbers of inducible nitric oxide synthase positive eosinophils. This eosinophil population plays a critical
role in the downregulation of T cell responses and ameliorating graft rejection. Depletion of eosinophils prior to
engraftment prevents co-stimulatory blockade-mediated lung allograft tolerance. These findings led to our
central hypothesis that early recruitment of eosinophils into the lung leads to allograft immunosuppression
through iNOS-dependent pathways. Towards this hypothesis we propose three Specific Aims to define the
cellular mechanism used by eosinophils to induce graft acceptance. In Aim 1 we propose to define the
physiology of iNOS production and mechanism/s of immunosuppression in the lung allograft through use of
eosinophil-specific iNOS pathway deficient mice, characterization of NO/ROS modification of T cells, and
regulation of iNOS by heme-oxygenase 1. In Aim 2 we will define the role of professional antigen presenting
cells in eosinophil-mediated immunosuppression by measuring eosinophil-specific mediators of that suppress
dendritic cell activity, bi-directional interactions of eosinophils and dendritic cells, and live imaging of synaptic
formation between these cells with T cells. In Aim 3 we will define the migratory patterns that contribute to
eosinophil-mediated tolerance. We will complete this through measuring the effect of co-stimulatory blockade
on eosinophil chemokine eotaxin-2 as well as determine the critical time point of eosinophil recruitment to the
lungs using inducible eosinophil depletion mice. Our data will provide novel insight into cellular immune
responses contributing to lung allograft tolerance and may shed light on the design of novel therapeutic
strategies that are not currently being explored.

## Key facts

- **NIH application ID:** 10245321
- **Project number:** 5R01AI145108-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Elizabeth A Jacobsen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $512,800
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10245321

## Citation

> US National Institutes of Health, RePORTER application 10245321, The Role of Eosinophils in the Lung Allograft (5R01AI145108-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10245321. Licensed CC0.

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