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

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

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

    Research output: Contribution to journalJournal articleCommunication

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

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. CD4+/CD8+ double-positive T cells: more than just a developmental stage?

    Research output: Contribution to journalJournal articleResearchpeer-review

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

    Research output: Contribution to journalJournal articleResearchpeer-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
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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 languageEnglish
JournalJournal of Leukocyte Biology
Volume108
Issue number3
Pages (from-to)983-998
Number of pages16
ISSN0741-5400
DOIs
Publication statusPublished - Sep 2020

    Research areas

  • IFN-β, LPS, macrophage, PD1, soluble PD-L1, Trophoblast

ID: 59857213