Immunomodulatory effects of adipose-derived mesenchymal stem cells on the gene expression of major transcription factors of T cell subsets

Int Immunopharmacol. 2014 Jun;20(2):316-21. doi: 10.1016/j.intimp.2014.03.003. Epub 2014 Apr 3.

Abstract

It has been proposed that the immunomodulatory properties of mesenchymal stem cells (MSCs) play a crucial role in establishing and leading T lymphocytes, especially Th cell subsets, toward different functional subsets. To determine the effect of the immunomodulatory and regulatory functions of adipose-derived MSCs (AD-MSCs) on C57BL/6 spleen-isolated mononuclear cells (Spleen-MNCs), the gene expression of well-known effector and regulatory Th cell-related transcription factors, i.e., t-bet, GATA-3, Ror-γt and Foxp3, and their related cytokines, i.e., IFN-γ for Th1 cells, IL-4 for Th2 cells, IL-17 for Th17 cells and IL-10 and TGF-β for regulatory T cells, was studied using a co-culture condition system. The proliferation index of Spleen-MNCs was analyzed using a cell proliferation assay kit that utilized the CFSE staining method. Our findings indicate that AD-MSCs greatly impact the up-regulation of immunomodulatory cytokines, such as TGF-β (p<0.001), and the down-regulation of inflammatory cytokines, such as IFN-γ (p<0.005), and transcription factors, such as t-bet (p<0.001). Considering the immunomodulatory effects of MSCs in the differentiation of Th cell subsets, understanding and harnessing this property of MSCs could be a powerful strategy in the treatment of inflammatory autoimmune diseases such as multiple sclerosis.

Keywords: AD-MSCs; Autoimmunity; Cell subsets; Immunomodulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / immunology*
  • Animals
  • Cell Communication
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / metabolism
  • Gene Expression Regulation
  • Immunomodulation
  • Inflammation Mediators / metabolism
  • Lymphocyte Activation
  • Mesenchymal Stem Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Spleen / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Cytokines
  • Inflammation Mediators
  • Transcription Factors