Expression of a mutant CD47 protects against phagocytosis without inducing cell death or inhibiting angiogenesis.
Cell Rep Med
; 5(3): 101450, 2024 Mar 19.
Article
en En
| MEDLINE
| ID: mdl-38508139
ABSTRACT
CD47 is a ligand of SIRPα, an inhibitory receptor expressed by macrophages, dendritic cells, and natural killer (NK) cells, and, therefore, transgenic overexpression of CD47 is considered an effective approach to inhibiting transplant rejection. However, the detrimental effect of CD47 signaling is overlooked when exploring this approach. Here, we construct a mutant CD47 by replacing the transmembrane and intracellular domains with a membrane anchor (CD47-IgV). In both human and mouse cells, CD47-IgV is efficiently expressed on the cell surface and protects against phagocytosis in vitro and in vivo but does not induce cell death or inhibit angiogenesis. Furthermore, hematopoietic stem cells expressing transgenic CD47-IgV show no detectable alterations in engraftment or differentiation. This study provides a potentially effective means of achieving transgenic CD47 expression that may help to produce gene-edited pigs for xenotransplantation and hypoimmunogenic pluripotent stem cells for regenerative medicine.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antígeno CD47
/
Angiogénesis
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep Med
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos