title: Mesenchymal Stromal Cell-Like Cells Set the Balance of Stimulatory and Inhibitory Signals in Monocyte-Derived Dendritic Cells.
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.
authors: 1 Department of Immunology, Medical and Health Science Center, University of Debrecen , Debrecen, Hungary .
authors: Ildikó
authors: I
authors: Bacskai
authors: 1 Department of Immunology, Medical and Health Science Center, University of Debrecen , Debrecen, Hungary .
authors: Anett
authors: A
authors: Mázló
authors: 2 Department of Rheumatology, Beth Israel Deaconess Medical Center , Boston, Massachusetts.
authors: Katalin
authors: K
authors: Kis-Tóth
authors: 1 Department of Immunology, Medical and Health Science Center, University of Debrecen , Debrecen, Hungary .
authors: Attila
authors: A
authors: Szabó
authors: 3 Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen , Debrecen, Hungary .
authors: György
authors: G
authors: Panyi
authors: 4 Institute of Enzymology , Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary .
authors: Balázs
authors: B
authors: Sarkadi
authors: 4 Institute of Enzymology , Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary .
authors: Ágota
authors: Á
authors: Apáti
authors: 1 Department of Immunology, Medical and Health Science Center, University of Debrecen , Debrecen, Hungary .
authors: Éva
authors: É
authors: Rajnavölgyi
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines