# Donor nonclassical monocytes mediate primary graft dysfunction and remote organ injury following lung transplant surgery

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $717,581

## Abstract

Project Summary
Lung transplantation is a life-saving treatment for people with severe lung disease. However, complications like
primary graft dysfunction (PGD) can occur due to ischemia reperfusion injury (IRI), which limits the success of
the transplant. PGD often affects other organs, like the kidneys, and can reduce the 5-year survival rate of
patients to less than 50%. Currently, treatments that deplete neutrophils, which contribute to PGD, are not
feasible due to their role in fighting infections.
The goal of this research project is to build on seminal findings during the prior funding cycle and better
understand how donor nonclassical monocytes contribute to PGD and injury in other organs. By understanding
the mechanisms behind PGD and remote organ injury, new therapeutic strategies to improve outcomes for lung
transplant recipients can be developed.
The first aim of the project is to investigate how classical monocytes in the recipients contribute to the retention
of donor nonclassical monocytes in other organs, leading to injury. Donor nonclassical monocytes migrate to
other organs, such as the kidneys and native lung, and cause damage similar to what is observed in the lung
allograft. We will study the pathways involved in classical monocyte activation and how they promote donor
nonclassical monocyte retention. Through these experiments, we aim to identify potential therapeutic targets to
prevent bystander organ injury.
The second aim is to understand the different mechanisms of activation and contrasting roles of donor and
recipient nonclassical monocytes in the development of PGD. We have found that donor nonclassical monocytes,
but not recipient nonclassical monocytes, contribute to lung allograft damage. We investigate the factors that
activate donor nonclassical monocytes during the phases of ischemia-reperfusion and their impact on tissue
injury. Additionally, we will study the involvement of mitochondrial reactive oxygen species released from donor
lung epithelium in upregulating TLR transcription and cell surface translocation on donor nonclassical monocytes.
We will also explore our exciting new discovery that Nod2 signaling can promote the conversion of recipient
inflammatory classical monocytes into anti-inflammatory nonclassical monocytes. The goal is to develop new
therapeutic approaches to mitigate PGD and promote resolution of lung injury.
Overall, this study aims to provide a comprehensive understanding of the interactions between donor
nonclassical monocytes, host classical monocytes, and other immune cells in the context of PGD and bystander
organ injury. The insights gained will help develop new strategies to improve outcomes in lung transplantation
and minimize the impact of PGD on graft and recipient survival.

## Key facts

- **NIH application ID:** 10817533
- **Project number:** 2R01HL145478-06
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ankit Bharat
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $717,581
- **Award type:** 2
- **Project period:** 2019-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817533

## Citation

> US National Institutes of Health, RePORTER application 10817533, Donor nonclassical monocytes mediate primary graft dysfunction and remote organ injury following lung transplant surgery (2R01HL145478-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10817533. Licensed CC0.

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