1. The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft.
- Author
-
Li, Xiao, Turaga, Diwakar, Li, Rich G., Tsai, Chang-Ru, Quinn, Julianna N., Zhao, Yi, Wilson, Ruby, Carlson, Katherine, Wang, Jun, Spinner, Joseph A., Hickey, Edward J., Adachi, Iki, and Martin, James F.
- Subjects
- *
KILLER cells , *HOMOGRAFTS , *CELL populations , *MACROPHAGES , *RNA sequencing , *LIFE spans , *PHAGOCYTOSIS - Abstract
BACKGROUND: Much of our knowledge of organ rejection after transplantation is derived from rodent models. METHODS: We used single-nucleus RNA sequencing to investigate the inflammatory myocardial microenvironment in human pediatric cardiac allografts at different stages after transplantation. We distinguished donor- from recipient-derived cells using naturally occurring genetic variants embedded in single-nucleus RNA sequencing data. RESULTS: Donor-derived tissue resident macrophages, which accompany the allograft into the recipient, are lost over time after transplantation. In contrast, monocyte-derived macrophages from the recipient populate the heart within days after transplantation and form 2 macrophage populations: recipient MP1 and recipient MP2. Recipient MP2s have cell signatures similar to donor-derived resident macrophages; however, they lack signatures of pro-reparative phagocytic activity typical of donor-derived resident macrophages and instead express profibrotic genes. In contrast, recipient MP1s express genes consistent with hallmarks of cellular rejection. Our data suggest that recipient MP1s activate a subset of natural killer cells, turning them into a cytotoxic cell population through feed-forward signaling between recipient MP1s and natural killer cells. CONCLUSIONS: Our findings reveal an imbalance of donor-derived and recipient-derived macrophages in the pediatric cardiac allograft that contributes to allograft failure. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF