Inhibition of immune synapse by altered dendritic cell actin distribution: a new pathway of mesenchymal stem cell immune regulation.
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.
Aldinucci
Alessandra
A
Department of Neurological Sciences, University of Florence, Florence, Italy.
Rizzetto
Lisa
L
Pieri
Laura
L
Nosi
Daniele
D
Romagnoli
Paolo
P
Biagioli
Tiziana
T
Mazzanti
Benedetta
B
Saccardi
Riccardo
R
Beltrame
Luca
L
Massacesi
Luca
L
Cavalieri
Duccio
D
Ballerini
Clara
C
D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D054992:Immunological Synapses / Q000276:immunology* / Q000648:ultrastructure; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron
D000199:Actins