Cytokine stimulation of the choriocarcinoma cell line JEG-3 leads to alterations in the HLA-G expression profile

Cell Immunol. 2020 Jun:352:104110. doi: 10.1016/j.cellimm.2020.104110. Epub 2020 Apr 7.

Abstract

The checkpoint molecule human leukocyte antigen (HLA)-G has restricted tissue expression, and plays a role in the establishment of maternal tolerance to the semi-allogenic fetus during pregnancy by expression on the trophoblast cells in the placenta. HLA-G exists in at least seven well-described mRNA isoforms, of which four are membrane-bound and three soluble. Regulation of the tissue expression of HLA-G and its isoforms is relatively unknown. Therefore, it is important to understand the regulation of HLA-G, and the HLA-G+ choriocarcinoma cell line JEG-3 is a widely used cellular model. We hypothesized that cytokines present in the microenvironment can regulate the HLA-G expression profile. In the present study, we systematically stimulated JEG-3 cells with various concentrations of IL-2, IL-4 IL-6, IL-10, IL-12, IL-15, IL-17A, TGF-β1, TNF-α and IFN-γ1b. The results suggest that IFN-γ plays a role in maintenance of HLA-G expression, while IL-10 might be involved in regulation of the isoform profile.

Keywords: Cancer; Cell line; Cytokine; HLA class Ib; HLA-G; Immune tolerance; Isoform; Preeclampsia; Pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Choriocarcinoma / immunology*
  • Cytokines / metabolism
  • Gene Expression / drug effects
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • HLA Antigens / metabolism
  • HLA-G Antigens / genetics*
  • HLA-G Antigens / immunology*
  • HLA-G Antigens / metabolism
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Immune Tolerance
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Transcriptome / immunology
  • Trophoblasts / metabolism
  • Tumor Microenvironment

Substances

  • Cytokines
  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • Interleukin-10
  • Interferon-gamma