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Published Online: 26 March 2015

Mesenchymal Stromal Cell-Like Cells Set the Balance of Stimulatory and Inhibitory Signals in Monocyte-Derived Dendritic Cells

Publication: Stem Cells and Development
Volume 24, Issue Number 15

Abstract

The major reservoir of human multipotent mesenchymal stem/stromal cells (MSCs) is the bone marrow (BM) with the capability to control hematopoietic stem cell development. The regenerative potential of MSCs is associated with enhanced endogenous repair and healing mechanisms that modulate inflammatory responses. Our previous results revealed that MSC-like (MSCl) cells derived from pluripotent human embryonic stem cells resemble BM-derived MSCs in morphology, phenotype, and differentiating potential. In this study, we investigated the effects of MSCl cells on the phenotype and functions of dendritic cells (DCs). To assess how antiviral immune responses could be regulated by intracellular pattern recognition receptors of DCs in the presence of MSCl cells, we activated DCs with the specific ligands of retinoic acid-inducible gene-I (RIG-I) helicases and found that activated DCs cocultured with MSCl cells exhibited reduced expression of CD1a and CD83 cell surface molecules serving as phenotypic indicators of DC differentiation and activation, respectively. However, RIG-I-mediated stimulation of DCs through specific ligands in the presence of MSCl cells resulted in significantly higher expression of the costimulatory molecules, CD80 and CD86, than in the presence of BM-MSCs. In line with these results, the concentration of IL-6, IL-10, and CXCL8 was increased in the supernatant of the DC-MSCl cocultures, while the secretion of TNF-α, CXCL10, IL-12, and IFNγ was reduced. Furthermore, the concerted action of mechanisms involved in the regulation of DC migration resulted in the blockade of cell migration, indicating altered DC functionality mediated by MSCl cell-derived signals and mechanisms resulting in a suppressive microenvironment.

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Published In

cover image Stem Cells and Development
Stem Cells and Development
Volume 24Issue Number 15August 1, 2015
Pages: 1805 - 1816
PubMed: 25808140

History

Published in print: August 1, 2015
Published ahead of print: 29 April 2015
Published online: 26 March 2015
Accepted: 23 March 2015
Received: 28 October 2014

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Ildikó Bacskai
Department of Immunology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Anett Mázló
Department of Immunology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Katalin Kis-Tóth
Department of Rheumatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Attila Szabó
Department of Immunology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
György Panyi
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Balázs Sarkadi
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
Ágota Apáti*
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
Éva Rajnavölgyi*
Department of Immunology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.

Notes

*
These authors contributed equally to this work.
Address correspondence to:Prof. Éva RajnavölgyiDepartment of ImmunologyMedical and Health Science CenterUniversity of Debrecen1 Egyetem sqDebrecen H-4032Hungary
E-mail: [email protected]

Author Disclosure Statement

No competing financial interests exist.

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