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Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function

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DOI

  1. Niels Borregaard, M.D. (1951-2017)

    Publikation: Bidrag til tidsskriftTidsskriftartikelFormidling

  2. Smoking reduces circulating CD26hiCD161hi MAIT cells in healthy individuals and patients with multiple sclerosis

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  4. Molecular and stimulus-response profiles illustrate heterogeneity between peripheral and cord blood-derived human mast cells

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Yong-Hong Zhang
  • Paulomi Aldo
  • Yuan You
  • Jiahui Ding
  • Janina Kaislasuo
  • Jesper F Petersen
  • Ellen Lokkegaard
  • Gang Peng
  • Michael J Paidas
  • Samantha Simpson
  • Lubna Pal
  • Seth Guller
  • Hong Liu
  • Ai Hua Liao
  • Gil Mor
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftJournal of Leukocyte Biology
Vol/bind108
Udgave nummer3
Sider (fra-til)983-998
Antal sider16
ISSN0741-5400
DOI
StatusUdgivet - sep. 2020

Bibliografisk note

©2020 Society for Leukocyte Biology.

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