IL-1β enhances human placenta-derived mesenchymal stromal cells ability to mediate Th1/Th2 and Th1/CD4+IL-10+ T cell balance and regulates its adhesion, proliferation and migration via PD-L1

Cell Immunol. 2020 Jun:352:104113. doi: 10.1016/j.cellimm.2020.104113. Epub 2020 Apr 13.

Abstract

Human placenta-derived mesenchymal stromal cells (hPMSCs) are promising candidates for the treatment of graft-versus-host disease (GVHD), which is associated with high IL-1β levels. In this study, the effects of IL-1β and hPMSCs on each other were investigated by analyzing the proportion of Th1, Th2 and CD4+IL-10+ T cells and PD-L1 expression, as well as the adhesion, migration, and proliferation of hPMSCs. The results showed that hPMSCs decreased IL-1β levels and downregulated Th1/Th2 and Th1/CD4+IL-10+ T cells ratios in the GVHD model. The in vitro results revealed that IL-1β strengthened the hPMSCs capacity to reduce the Th1/Th2 and Th1/CD4+IL-10+ T cell ratios, inhibited the adhesion and proliferation of hPMSCs and increased PD-L1 expression on hPMSCs via the JAK and NF-κB pathways. Overall, these findings suggested that hPMSCs alleviate GVHD by decreasing IL-1β level and maintaining the balance among different T cell subsets. IL-1β enhanced the ability of hPMSCs to balance different T cell subsets and inhibited hPMSCs adhesion and proliferation by regulating PD-L1 expression via the JAK and NF-κB pathways.

Keywords: IL-1β; Mesenchymal stromal cells (MSCs); PD-L1; Placenta; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / immunology*
  • B7-H1 Antigen / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Adhesion / immunology
  • Cell Differentiation / immunology
  • Cell Movement / immunology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Coculture Techniques
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / metabolism
  • Humans
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Interleukin-1beta / immunology*
  • Interleukin-1beta / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Placenta / cytology
  • Placenta / immunology*
  • Placenta / metabolism
  • Pregnancy
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • B7-H1 Antigen
  • Interleukin-1beta
  • Interleukin-10