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Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells MSCs
Published on: December 24, 2015
TNF-α modulates the immunosuppressive effects of MSCs on dendritic cells and T cells
Hemn Mohammadpour1, Ali Akbar Pourfathollah1, Mahin Nikougoftar Zarif2
1Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Abstract:
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.
Insights
Mesenchymal stem cells (MSCs) show altered immune effects based on cytokine environment. IFN-γ enhances MSC immunosuppression, while TNF-α reduces it by modulating dendritic cell and T cell functions.
Area of Science:
- Immunology
- Cell Biology
- Stem Cell Research
Background:
- Mesenchymal stem cells (MSCs) are multipotent progenitor cells with immunomodulatory properties.
- MSC functions, including immune suppression, are influenced by cytokines like interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α).
Purpose of the Study:
- To investigate how MSCs, activated by IFN-γ and TNF-α, affect dendritic cell (DC) differentiation and T cell responses.
- To analyze the impact of different cytokine microenvironments on MSC immunomodulatory capabilities.
Main Methods:
- Differentiated dendritic cells (DCs) in the presence of MSCs, TNF-α-activated MSCs, IFN-γ-activated MSCs, and combined IFN-γ & TNF-α-activated MSCs.
- Analyzed DC phenotypes, co-stimulatory/co-inhibitory molecule expression, and allogeneic T cell activation.
- Assessed Treg population and T cell polarization using flow cytometry and real-time PCR.
Main Results:
- IFN-γ-activated MSCs enhanced immunosuppression by inducing tolerogenic DCs with increased IDO expression and a higher Treg population.
- TNF-α-activated MSCs reduced immunomodulation, upregulating co-stimulatory molecules (ICOSL, HLA-DR) on DCs, downregulating PD-L1/PD-L2, and decreasing TGF-β/IL-10.
- TNF-α also inhibited T cell polarization into TH2 and Treg subsets.
Conclusions:
- MSC behavior and immunomodulatory functions are significantly altered by the cytokine microenvironment.
- IFN-γ enhances MSC immunosuppressive effects, whereas TNF-α diminishes them, highlighting the context-dependent nature of MSC-mediated immune modulation.
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