# The Role of Donor Innate Immune Responses in Regulating Alloimmunity after Heart Transplantation

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $636,632

## Abstract

PROJECT SUMMARY/ABSTRACT
The success of heart transplantation is limited by ischemia reperfusion injury-mediated primary graft dysfunction
and allograft rejection, two processes that may be immunologically linked. Current strategies to reduce graft
rejection and improve survival are mostly based on ablation of recipient immune cell populations. These
approaches are only modestly effective and carry high risks of life-threatening infections. An alternative and
potentially safer approach is to target immune pathways and cell populations within the donor graft that initiate
inflammatory responses and resultant alloreactivity. The ability to precisely control the initial immune response
following heart transplantation represents a promising approach to increase allograft tolerance and improve
clinical outcomes. Our recent work has identified that ferroptosis, a non-apoptotic form of inflammatory cell death
mediates the early inflammatory response after reperfusion of heart grafts. We have discovered that graft
endothelial cells and tissue-resident CCR2+ macrophages play important and complementary roles in promoting
the recruitment of inflammatory immune cells to the transplanted heart. In this proposal, we will use state-of-the-
art techniques, including intravital microscopy, single cell RNA sequencing and novel mouse strains to perform
studies that will 1) define mechanisms of cell death (Aim1), 2) evaluate the role of cell-specific inflammatory
cytokine signaling (Aim 2) and 3) examine the role of cardiac macrophage heterogeneity (Aim 3) in driving innate
inflammatory and alloimmune responses after heart transplantation. Our studies will lay the foundation for novel
therapy that will improve outcomes after cardiac transplantation.

## Key facts

- **NIH application ID:** 10405512
- **Project number:** 5R01HL151078-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Daniel Kreisel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $636,632
- **Award type:** 5
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405512

## Citation

> US National Institutes of Health, RePORTER application 10405512, The Role of Donor Innate Immune Responses in Regulating Alloimmunity after Heart Transplantation (5R01HL151078-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10405512. Licensed CC0.

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