Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function.
J Leukoc Biol
; 108(3): 983-998, 2020 09.
Article
en En
| MEDLINE
| ID: mdl-32386458
ABSTRACT
Decidual macrophages are in close contact with trophoblast cells during placenta development, and an appropriate crosstalk between these cellular compartments is crucial for the establishment and maintenance of a healthy pregnancy. During different phases of gestation, macrophages undergo dynamic changes to adjust to the different stages of fetal development. Trophoblast-secreted factors are considered the main modulators responsible for macrophage differentiation and function. However, the phenotype of these macrophages induced by trophoblast-secreted factors and the factors responsible for their polarization has not been elucidated. In this study, we characterized the phenotype and function of human trophoblast-induced macrophages. Using in vitro models, we found that human trophoblast-educated macrophages were CD14+ CD206+ CD86- and presented an unusual transcriptional profile in response to TLR4/LPS activation characterized by the expression of type I IFN-ß expression. IFN-ß further enhances the constitutive production of soluble programmed cell death ligand 1 (PD-L1) from trophoblast cells. PD-1 blockage inhibited trophoblast-induced macrophage differentiation. Soluble PD-L1 (sPD-L1) was detected in the blood of pregnant women and increased throughout the gestation. Collectively, our data suggest the existence of a regulatory circuit at the maternal fetal interface wherein IFN-ß promotes sPD-L1 expression/secretion by trophoblast cells, which can then initiate a PD-L1/PD-1-mediated macrophage polarization toward an M2 phenotype, consequently decreasing inflammation. Macrophages then maintain the expression of sPD-L1 by the trophoblasts through IFN-ß production induced through TLR4 ligation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trofoblastos
/
Embarazo
/
Diferenciación Celular
/
Antígeno B7-H1
/
Activación de Macrófagos
/
Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
J Leukoc Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos