摘要：SummaryMesenchymal stromal cell-like (MSCl) cells generated from human embryonic stem cells are considered to be an eligible cell line to model the immunomodulatory behavior of mesenchymal stromal cells (MSCs)in vitro. Dendritic cells (DCs) are essential players in the maintenance and restoration of the sensitive balance between tolerance and immunity. Here, the effects of MSCl cells on thein vitrodifferentiation of human monocytes into DCs were investigated. MSCl cells promote the differentiation of CTLA-4 expressing DCs via the production of all-trans retinoic acid (ATRA) functioning as a ligand of RARα, a key nuclear receptor in DC development. These semi-matured DCs exhibit an ability to activate allogeneic, naive T cells and polarize them into IL-10 + IL-17 + double-positive T helper cells in a CTLA-4-dependent manner. Mapping the molecular mechanisms of MSC-mediated indirect modulation of DC differentiation may help to expand MSCs' clinical application in cell-free therapies.Graphical abstractDisplay OmittedHighlights•Mesenchymal stromal cell-like cells alter moDC differentiation via RARα activation•Mesenchymal stromal cell-like cells express genes known to play role in ATRA synthesis•MoDCs, differentiated in the presence of MSCl-derived factors, express CTLA-4•CTLA-4+moDCs are able to induce polarization of IL-10- and IL-17-producing helper T cellsMolecular Biology; Immunology; Components of the Immune System; Stem Cells Research
