The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft.
Circulation
; 149(21): 1650-1666, 2024 May 21.
Article
en En
| MEDLINE
| ID: mdl-38344825
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trasplante de Corazón
/
Aloinjertos
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Rechazo de Injerto
/
Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
/
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Año:
2024
Tipo del documento:
Article