MSCs inhibit bone marrow-derived DC maturation and function through the release of TSG-6

Biochem Biophys Res Commun. 2014 Aug 8;450(4):1409-15. doi: 10.1016/j.bbrc.2014.07.001. Epub 2014 Jul 8.

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that are characterized by the ability to take up and process antigens and prime T cell responses. Mesenchymal stem cells (MSCs) are multipotent cells that have been shown to have immunomodulatory abilities, including inhibition of DC maturation and function in vivo and in vitro; however, the underlying mechanism is far from clear. In this study we found that MSCs can inhibit the maturation and function of bone marrow-derived DCs by releasing TSG-6. In the presence of MSCs, lower expression of mature DC surface phenotype (CD80, CD86, MHC-II, and CD11c) was observed. In addition, typical DC functions, such as the production of IL-12 and the ability to prime T cells, were decreased when co-cultured with MSCs. In contrast, knockdown of TSG-6 reduced the inhibitory effect of MSCs on DC. Moreover, we found that TSG-6 can suppress the activation of MAPKs, and NF-κB signaling pathways within DCs during Lipopolysaccharides (LPS) stimulation. In conclusion, we suggest that TSG-6 plays an important role in MSCs-mediated immunosuppressive effect on DC.

Keywords: Dendritic cells; Immunology; In vitro; Mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Adhesion Molecules / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / cytology*
  • Female
  • Interleukin-12 / metabolism
  • Lymphocyte Activation
  • MAP Kinase Signaling System
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • NF-kappa B / antagonists & inhibitors

Substances

  • Cell Adhesion Molecules
  • NF-kappa B
  • Tnfaip6 protein, mouse
  • Interleukin-12