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

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

doi:10.1016/j.isci.2021.102312

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

iScience. 2021 Mar 15;24(4):102312. doi: 10.1016/j.isci.2021.102312. eCollection 2021 Apr 23.

Authors

Anett Mázló^{1

2

3}, Ramóna Kovács^{1

2}, Noémi Miltner¹, Márta Tóth^{1

2}, Zoltán Veréb^{4

5}, Krisztina Szabó⁶, Ildikó Bacskai¹, Kitti Pázmándi¹, Ágota Apáti⁷, Tamás Bíró¹, Krisztián Bene^{1

8}, Éva Rajnavölgyi¹, Attila Bácsi¹

Affiliations

¹ Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hajdú-Bihar County 4032, Hungary.
² Doctoral School of Molecular Cellular and Immune Biology, University of Debrecen, Debrecen, Hajdú-Bihar County 4032, Hungary.
³ MTA-DE Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Debrecen, Hajdú-Bihar County 4032, Hungary.
⁴ Regenerative Medicine and Cellular Pharmacology Research Laboratory, Department of Dermatology and Allergology, University of Szeged, Szeged, Csongrád-Csanád County 6720, Hungary.
⁵ Research Institute of Translational Biomedicine, Department of Dermatology and Allergology, University of Szeged, Szeged, Csongrád-Csanád County 6720, Hungary.
⁶ Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hajdú-Bihar County 4032, Hungary.
⁷ Institute of Enzymology, Research Centre for Natural Sciences, Budapest 1117 Hungary.
⁸ Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hajdú-Bihar County 4032, Hungary.

Abstract

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.

Keywords: Components of the Immune System; Immunology; Molecular Biology; Stem Cells Research.