Mesenchymal Stem Cells Upregulate the Expression of PD-L1 But Not VDR in Dendritic Cells

Mesenchymal stem cells (MSCs) show immunomodulatory functions. But the exact mechanism underlying these activities of MSCs is still not completely understood. There have been a few studies which have assessed the effects of these cells on dendritic cells (DCs) function. Given the importance of programmed cell death receptor-1 (PD-L1) and vitamin D receptor (VDR) expression in induction of tolerance in DCs, we were encouraged to investigate if one of the immunomodulatory functions of MSCs could be inducing upregulation of PD-L1 and VDR on DCs or not.

DCs were co-cultured with MSCs or treated with them in transwell plates in the presence or absence of Lipopolysaccharide (LPS). Expression of PD-L1 and VDR mRNA and proteins in treated DCs were assessed by Real-time PCR and Western blot techniques. Furthermore, treated DCs were co-cultured with allogeneic T-cells, and T-cell proliferation and cytokine secretions in co-culture supernatants were assessed.

The results showed that PD-L1 but not VDR expression is significantly upregulated in the DCs co-cultured with MSCs. Furthermore, cell-to-cell contact and also presence of maturation inducers like LPS is necessary for this function. Moreover, our results indicated that MSCs could induce tolerogenic DCs (TolDCs) which could decrease the secretion of IL-2 by T-cells and inhibit T-cell proliferation as well as increase secretion of IL-10.

Overall, our results show that MSCs may have several suppressive effects on immune responses by induction of TolDCs expressing more PD-L1 immunomodulatory molecule and change the cytokines profile of DCs and T-cells.