Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function
Research output: Contribution to journal › Journal article › Research › peer-review
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-β expression. IFN-β 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-β 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-β production induced through TLR4 ligation.
Original language | English |
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Journal | Journal of Leukocyte Biology |
Volume | 108 |
Issue number | 3 |
Pages (from-to) | 983-998 |
Number of pages | 16 |
ISSN | 0741-5400 |
DOIs | |
Publication status | Published - 2020 |
- IFN-β, LPS, macrophage, PD1, soluble PD-L1, Trophoblast
Research areas
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190653/pdf/nihms-1608639.pdf
Accepted author manuscript
ID: 260202558