The final manifestation of immune responses is a result of a complex interaction of phenotypically and functionally different cell populations. Mesenchymal stromal cell-like (MSCl) cells are considered to be an eligible cell line to model the immunomodulatory behavior of mesenchymal stromal cells (MSCs) in vitro. One possible target of MSC-mediated regulation is the population of dendritic cells playing a determining role in shaping the outcome of effector cell responses. However, it is still uncovered how monocyte-derived dendritic cell (moDC) populations drive the polarization of helper T cells (Th) in the presence of MSCI-conditioned medium (MSCI-CM) or MSCI cells.
We induced the differentiation of moDCs in co-cultured with MSCI cells or in the presence of MSCI-CM, IL-4, and GM-CSF. MoDCs were characterized by flow cytometry while their cytokine production was measured by Human XL Cytokine Array Kit or ELISA. The polarization of T cell response was monitored by ELISPOT and flow cytometry.
Here, the effects of MSCl cells on the in vitro differentiation of human monocytes into DCs were investigated. MSCl cells promote the differentiation of CD14, DC-SIGN, CD86, MHC- II, and CTLA-4 expressing monocyte-derived cells partially via all-trans retinoic acid production (ATRA) functioning as a ligand of RARa, a key nuclear receptor in DC development. The presence of MSCI cells or MSCI-CM during the moDC differentiation resulted in the altered secretion of a wide array of inflammatory and immunsuppressive cytokines as well. 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.
Thus, these data outline a novel mechanism mediated by MSCI cells, which drives moDC differentiation to a regulatory phenotype. Additionally, mapping the molecular mechanisms of MSC-mediated indirect modulation of DC differentiation may help to expand MSCs’ clinical application in cell-free therapies.
I started my studies at the University of Debrecen. I was graduated with a Bachelor of Science Degree in Biology and a Master’s Molecular biologist Degree in Immunology, Cell- and Microbiology. I advanced my Doctorate studies at the doctoral school of Molecular Cell- and Immunobiology. I worked as a junior research fellow for the Hungarian Academy of Sciences. I am currently working as a researcher and tutor in the position of a lecturer assistant at the Department of Immunology. Our research group focuses on the dendritic cell (DC) biology, more precisely, the differentiation process of dendritic cells or macrophages from monocytes.
A great target to examine the fine-tuned synergy of DCs with other immunomodulatory cells is the mesenchymal stem/stromal cells (MSC). We attempted to reveal the complex interactions between the DCs and MSCs, which could be crucial for understanding the molecular mechanisms in the pathogeneses of immune-related diseases.