MSC-like cells increase ability of monocyte-derived dendritic cells to polarize IL-17-/IL-10-producing T cells via CTLA-4

• Main Authors: Anett Mázló, Ramóna Kovács, Noémi Miltner, Márta Tóth, Zoltán Veréb, Krisztina Szabó, Ildikó Bacskai, Kitti Pázmándi, Ágota Apáti, Tamás Bíró, Krisztián Bene, Éva Rajnavölgyi, Attila Bácsi
• Format: Article
• Language: English
• Published: Elsevier 2021-04-01
• Series: iScience
• Subjects: Molecular Biology; Immunology; Components of the Immune System; Stem Cells Research
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004221002807

Summary: Mesenchymal 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 the in vitro differentiation 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.