Abstract
Bone-marrow-derived mesenchymal stem cells (MSCs) have been shown to possess immunosuppressive properties, e.g., by inhibiting T cell proliferation. Activated T cells can also enhance the immunosuppression ability of MSCs. The precise mechanisms underlying MSC-mediated immunosuppression remain largely undefined, although both cell-cell contact and soluble factors have been implicated; nor is it clear how the immunosuppressive property of MSCs is modulated by T cells. Using MSCs isolated from mouse bone marrow, we show here that interferon gamma (IFNγ), a well-known proinflammatory cytokine produced by activated T cells, plays an important role in priming the immunosuppressive property of MSCs. Mechanistically, IFNγ acts directly on MSCs and leads to up-regulation of B7-H1, an inhibitory surface molecule in these stem cells. MSCs primed by activated T cells derived from IFNγ−/− mouse exhibited dramatically reduced ability to suppress T cell proliferation, a defect that can be rescued by supplying exogenous IFNγ. Moreover, siRNA-mediated knockdown of B7-H1 in MSCs abolished immunosuppression by these cells. Taken together, our results suggest that IFNγ plays a critical role in triggering the immunosuppresion by MSCs through up-regulating B7-H1 in these cells, and provide evidence supporting the cell-cell contact mechanism in MSC-mediated immunosuppression.
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Acknowledgements
We thank Dr Yi Zhang (Department of Cell Biology, Institute of Basic Medical Sciences, Beijing, China) for helpful discussions. This work was supported by National Basic Research Program of China (Grant No. 2005CB522705-3), National Natural Science Foundation of China (Grant No. 30671945), Science and Technology Commission of Shanghai Municipality (No. 06JC14044 and 07JC14070), Shanghai Leading Academic Discipline Project (T0206), Shanghai Institute of Immunology Academic Project (No. 07-A04, to Ningli Li) and Leading Academic discipline project (IRT0637, Education ministry of China).
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Sheng, H., Wang, Y., Jin, Y. et al. A critical role of IFNγ in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1. Cell Res 18, 846–857 (2008). https://doi.org/10.1038/cr.2008.80
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DOI: https://doi.org/10.1038/cr.2008.80
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