The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft.
Circulation
; 149(21): 1650-1666, 2024 May 21.
Article
in 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Heart Transplantation
/
Allografts
/
Graft Rejection
/
Macrophages
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
Circulation
Year:
2024
Document type:
Article
Country of publication:
United States