Priming of macrophage by glycosphingolipids from extracellular vesicles facilitates immune tolerance for embryo-maternal crosstalk

Tzu Chi Lo, Jing Yan Cheng, Chien Wei Lee, Jung Tung Hung, Chun Cheng Lin, Hsiao Fong Yeh, Bei Chia Yang, Yenlin Huang, Hsien Ming Wu*, Alice L. Yu, John Yu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

Glycosphingolipids (GSLs) display diverse functions during embryonic development. Here, we examined the GSL profiles of extracellular vesicles (EVs) secreted from human embryonic stem cells (hESCs) and investigated their functions in priming macrophages to enhance immune tolerance of embryo implantation. When peripheral blood mononuclear cells were incubated with ESC-secreted EVs, globo-series GSLs (GHCer, SSEA3Cer, and SSEA4Cer) were transferred via EVs into monocytes/macrophages. Incubation of monocytes during their differentiation into macrophages with either EVs or synthetic globo-series GSLs induced macrophages to exhibit phenotypic features that imitate immune receptivity, i.e., macrophage polarization, augmented phagocytic activity, suppression of T cell proliferation, and the increased trophoblast invasion. It was also demonstrated that decidual macrophages in first-trimester tissues expressed globo-series GSLs. These findings highlight the role of globo-series GSLs via transfer from EVs in priming macrophages to display decidual macrophage phenotypes, which may facilitate healthy pregnancy.

Original languageEnglish
Pages (from-to)2447-2459.e5
JournalDevelopmental Cell
Volume58
Issue number22
DOIs
StatePublished - 20 11 2023
Externally publishedYes

Bibliographical note

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords

  • decidual macrophages
  • embryo-maternal crosstalk
  • extracellular vesicles
  • glycosphingolipids
  • human embryonic stem cells
  • Humans
  • Immune Tolerance
  • Leukocytes, Mononuclear
  • Macrophages
  • Pregnancy
  • Glycosphingolipids
  • Female
  • Cell Differentiation

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