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Trophoblast‐secreted soluble‐PD‐L1 modulates macrophage polarization and function
Author(s) -
Zhang YongHong,
Aldo Paulomi,
You Yuan,
Ding Jiahui,
Kaislasuo Janina,
Petersen Jesper F,
Lokkegaard Ellen,
Peng Gang,
Paidas Michael J.,
Simpson Samantha,
Pal Lubna,
Guller Seth,
Liu Hong,
Liao Ai Hua,
Mor Gil
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.1a0420-012rr
Subject(s) - trophoblast , biology , microbiology and biotechnology , cd14 , macrophage polarization , macrophage , decidua , secretion , cd163 , cd86 , placenta , immunology , endocrinology , fetus , in vitro , t cell , immune system , biochemistry , pregnancy , genetics
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.