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- Title
A critical role of IFNγ in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1.
- Authors
Sheng, Huiming; Wang, Ying; Jin, Yuqing; Zhang, Qiuyu; Zhang, Yan; Wang, Li; Shen, Baihua; Yin, Shuo; Liu, Wei; Cui, Lei; Li, Ningli
- 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.Cell Research (2008) 18:846–857. doi: 10.1038/cr.2008.80; published online 8 July 2008
- Publication
Cell Research, 2008, Vol 18, Issue 8, p846
- ISSN
1001-0602
- Publication type
Academic Journal
- DOI
10.1038/cr.2008.80