TNF-α modulates the immunosuppressive effects of MSCs on dendritic cells and T cells

• Effects of pre-activated MSCs on phenotypes and functions of DCs differentially change regarding to different cytokines
• TNF-α decreases the immunosuppressive effects of MSCs on DCs and T cells.
• IFN-γ and IFN-γ & TNF-α increase immunosuppressive effects of MSCs.

Mesenchymal stem cells are progenitor cells that have capabilities to differentiate different cell types. Also, MSCs possess immune suppressive effects on DC differentiation and T cell activation through a wide range of soluble factors and receptors. The properties of MSCs change through activation of cytokines particularly IFN-γ and TNF-α. The DC phenotypes and functions including the expression of co-stimulatory and co-inhibitory molecules and capabilities of DCs to induce allogeneic activation of CFSE-labeled splenocytes as well as cytokine production when they were differentiated in the presence of MSCs, TNF-α activated MSCs, IFN-γ activated MSCs and IFN-γ & TNF-α activated MSCs were analyzed. Treg population and T cell polarization were investigated using flowcytometry and real-time PCR respectively. Here, we showed that IFN-γ slightly enhances immunosuppressive effects of MSCs on immune system through induction tolerogenic DCs with elevated expression of IDO and increasing Treg population. Conversely, TNF-α decreases immunomodulation properties of MSCs on immune cells through the enhancement of co-stimulatory molecules such as ICOSL and HLA-DR, reduction of PDL-1 and PDL-2 expression and decrease of TGF-β and IL-10 in DCs as well as inhibition of T cell polarization into TH2 and Treg. Taken together, these data showed crucial effects of microenvironments on MSC behaviors indicating that functions of MSCs differentially altered in the presence of different cytokines.