Past Funded Research Project РTransplant Immunology 

Roles of Cardiac and Hepatic Macrophage Subsets in Immune Tolerance

Primary Investigators: Dilini Soysa

Institution: The University of Washington at Seattle

Funding began in 2017.

This study was funded in 2017, with a focus on research of the role that a very specific cell group plays in the rejection of a transplanted heart.

Please read below to learn more about this research project or click here to view the final report.

The research aims at understanding why heart transplants are less tolerated compared to other organ transplants such as the liver. We plan to identify the role of immune cells, specifically macrophages in the transplanted organ that may play a role in determining the extent of transplant tolerance. Early transplant rejection episodes are a major risk factor in developing cardiac allograft vasculopathy. Cardiac allograft vasculopathy substantially reduces the health and survival of transplant patients.

Our main question is does the macrophages in the transplant play a role in tolerance? There are two main groups of macrophages in organs. One group originates during the embryo stage and maintain throughout life while the other group originates from adult bone marrow. So far those two groups are indistinguishable in organs and their roles in inflammation are unknown. Our goal is to label those two groups of macrophages using genetically engineered mice and study their immune roles in heart and liver inflammation as well as in a transplant model.

Our work will reveal the immune roles of the two different macrophage groups during inflammation and their contribution to heart transplant tolerance. If a group of macrophages is better at increasing tolerance, they will serve as potential cell therapy to increase initial heart transplant tolerance. Also, we can find novel ways to intervene and modify the other group of macrophages so that they also could potentially contribute to increased tolerance. Overall the long-term impact of this work is to find graft-based strategies to increase transplant tolerance and thereby decrease the cardiac allograft vasculopathy incidents.

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