MSC-like Cells Increase Ability of Monocyte-derived Dendritic Cells to Polarize IL-17-/IL-10-producing T cells Via CTLA-4

Overview

Journal iScience

Publisher Cell Press

Date 2021 Apr 15

PMID 33855282

Citations 6

Authors

Anett Mazlo

Ramona Kovacs

Noemi Miltner

Marta Toth

Zoltan Vereb

Krisztina Szabo

Ildiko Bacskai

Kitti Pazmandi

Agota Apati

Tamas Biro

Krisztian Bene

Eva Rajnavolgyi

Attila Bacsi

Affiliations

Soon will be listed here.

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) . 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 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.

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