miR-155 regulates immune modulatory properties of mesenchymal stem cells by targeting TAK1-binding protein 2.

The Journal of biological chemistry 2013 Apr 19

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MSCs possess potent immunosuppressive capacity. We have reported that mouse MSCs inhibit T cell proliferation and function via nitric oxide. This immune regulatory capacity of MSCs is induced by the inflammatory cytokines IFNγ together with either TNFα or IL-1β. This effect of inflammatory cytokines on MSCs is extraordinary; logarithmic increases in the expression of iNOS and chemokines are often observed. To investigate the molecular mechanisms underlying this robust effect of cytokines, we examined the expression of microRNAs in MSCs before and after cytokine treatment. We found that miR-155 is most significantly up-regulated. Furthermore, our results showed that miR-155 inhibits the immunosuppressive capacity of MSCs by reducing iNOS expression. We further demonstrated that miR-155 targets TAK1-binding protein 2 (TAB2) to regulate iNOS expression. Additionally, knockdown of TAB2 reduced iNOS expression. In summary, our study demonstrated that miR-155 inhibits the immunosuppressive capacity of MSCs by reducing iNOS expression by targeting TAB2. Our data revealed a novel role of miR-155 in regulating the immune modulatory activities of MSCs.

Citation

Chunliang Xu, Guangwen Ren, Gang Cao, Qing Chen, Peishun Shou, Chunxing Zheng, Liming Du, Xiaoyan Han, Menghui Jiang, Qian Yang, Liangyu Lin, Guan Wang, Pengfei Yu, Xin Zhang, Wei Cao, Gary Brewer, Ying Wang, Yufang Shi. miR-155 regulates immune modulatory properties of mesenchymal stem cells by targeting TAK1-binding protein 2. The Journal of biological chemistry. 2013 Apr 19;288(16):11074-9