Extracellular vesicles released by myeloid-derived suppressor cells from pregnant women modulate adaptive immune responses

Cell Immunol. 2021 Mar:361:104276. doi: 10.1016/j.cellimm.2020.104276. Epub 2020 Dec 24.

Abstract

Immunological pregnancy complications are a main challenge in reproductive medicine. Mechanisms regulating the adaptation of the maternal immune system to pregnancy are incompletely understood and therapeutic options limited. Myeloid derived suppressor cells (MDSC) are immune-modulatory cells expanding during healthy pregnancy and seem to play a crucial role for maternal-fetal tolerance. Recent studies showed that exosomes produced by MDSC have immune-modulatory effects corresponding to their parental cells under different pathological conditions. Here, we investigated immunological effects of exosomes of GR-MDSC during pregnancy. Isolated GR-MDSC exosomes from peripheral blood of pregnant women were tested for functionality in different in vitro assays. We show that GR-MDSC exosomes exhibited profound immune-modulatory effects such as suppression of T-cell proliferation, T helper 2 (Th2)-cell polarization, induction of regulatory T-cells and inhibition of lymphocyte cytotoxicity. Our results confirm that MDSC-derived exosomes functionally correspond to their parental cells and identify them as an interesting therapeutic target for immunological pregnancy complications.

Keywords: Extracellular vesicles; MDSC; Pregnancy; Th-cells; Tregs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Adaptive Immunity / physiology
  • Adult
  • Exosomes / immunology
  • Extracellular Vesicles / immunology*
  • Extracellular Vesicles / metabolism
  • Female
  • Granulocytes / immunology
  • Humans
  • Immune Tolerance / immunology
  • Immunity, Humoral / immunology
  • Lymphocyte Activation / immunology
  • Myeloid-Derived Suppressor Cells / immunology*
  • Myeloid-Derived Suppressor Cells / metabolism
  • Pregnancy / immunology*
  • Pregnant Women
  • T-Lymphocytes, Regulatory / immunology
  • Th2 Cells / immunology
  • Young Adult