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Inhibition of immune synapse by altered dendritic cell actin distribution: a new pathway of mesenchymal stem cell immune regulation.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2010 Nov 01; Vol. 185 (9), pp. 5102-10. Date of Electronic Publication: 2010 Oct 01. - Publication Year :
- 2010
-
Abstract
- Immune synapse formation between dendritic cells (DCs) and T cells is one of the key events in immune reaction. In immunogenic synapses, the presence of fully mature DCs is mandatory; consequently, the modulation of DC maturation may promote tolerance and represents a valuable therapeutic approach in autoimmune diseases. In the field of cell therapy, bone marrow mesenchymal stem cells (MSCs) have been extensively studied for their immunoregulatory properties, such as inhibiting DC immunogenicity during in vitro differentiation and ameliorating in vivo models of autoimmune diseases (e.g., experimental allergic encephalomyelitis). MSCs seem to play different roles with regard to DCs, depending on cell concentration, mechanism of stimulation, and accompanying immune cells. The aim of this work was to elucidate the immunogenic effects of MSC/DC interactions during DC activation (LPS stimulation or Ag loading). Human monocyte-derived DCs, bone marrow-derived MSCs, and circulating lymphocytes obtained from healthy donors, as well as the laboratory-generated influenza virus hemagglutinin-derived peptide, aa 306-318 peptide-specific T cell line were used for this study. We demonstrate that MSCs mediate inhibition of DC function only upon cell-cell contact. Despite no modification observed in cell phenotype or cytokine production, MSC-treated DCs were unable to form active immune synapses; they retained endocytic activity and podosome-like structures, typical of immature DCs. The transcriptional program induced by MSC-DC direct interaction supports at the molecular pathway level the phenotypical features observed, indicating the genes involved into contact-induced rearrangement of DC cytoskeleton.
- Subjects :
- Actins ultrastructure
Cell Communication genetics
Cell Separation
Cells, Cultured
Coculture Techniques
Cytoskeleton immunology
Cytoskeleton metabolism
Cytoskeleton ultrastructure
Dendritic Cells metabolism
Dendritic Cells ultrastructure
Flow Cytometry
Gene Expression
Gene Expression Profiling
Humans
Image Processing, Computer-Assisted
Immunohistochemistry
Immunological Synapses ultrastructure
Lymphocyte Activation immunology
Mesenchymal Stem Cells ultrastructure
Microscopy, Confocal
Microscopy, Electron, Transmission
Microscopy, Immunoelectron
Actins metabolism
Cell Communication immunology
Dendritic Cells immunology
Immunological Synapses immunology
Mesenchymal Stem Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 185
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 20889545
- Full Text :
- https://doi.org/10.4049/jimmunol.1001332