JBC：miR-155对间充质干细胞的免疫调节功能发挥重要调节作用

    近日，国际学术期刊《Journal of Biological Chemistry》在线发表了健康所时玉舫研究组题为“MiR-155 Regulates Immune Modulatory Properties of Mesenchymal Stem Cells by Targeting TAK1-binding Protein 2”的研究论文，报道了miR-155在间充质干细胞免疫抑制功能中的重要调节功能。

    间充质干细胞是在人体内广泛存在的一类成体干细胞，具有多向分化潜能，在组织稳态中发挥着重要作用，在再生医学领域中具有广泛的应用前景。近年来的研究证明，间充质干细胞对免疫系统具有广泛的抑制功作用。时玉舫研究组以前研究发现，小鼠间充质干细胞在受到炎症因子刺激后，表达大量的iNOS和趋化因子。T细胞在趋化因子的作用下迁移到间充质干细胞周围，受到NO作用，其增值受到抑制。近年来的研究发现，miRNA参与并调节众多生物学过程，该研究旨在揭示miRNA在间充质干细胞免疫抑制中的作用。

    博士研究生徐春亮等发现，间充质干细胞受到炎症因子刺激后，上调miR-155的表达。接下来研究发现，miR-155可以调节间充质干细胞对T细胞增殖的抑制作用。miR-155可以降低炎症因子诱导的iNOS表达，降低NO的浓度，从而发挥对间充质干细胞免疫抑制功能的调节作用。进一步研究发现，miR-155是通过直接作用于TAB2，下调其表达，从而发挥对iNOS的调节作用。该研究首次揭示了miRNA在间充质干细胞的免疫调节功能中调控作用，并为今后间充质干细胞的临床应用提供了重要参考。

    该研究得到了中国科学院战略性先导科技专项，国家科技部，国家自然科学基金委，及上海市科委的资助。

doi:10.1074/jbc.M112.414862
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MiR-155 Regulates Immune Modulatory Properties of Mesenchymal Stem Cells by Targeting TAK1-binding Protein 2

Chunliang Xu1, Guangwen Ren2, Gang Cao1, Qing Chen1, Peishun Shou1, Chunxing Zheng1, Liming Du1, Xiaoyan Han1, Menghui Jiang1, Qian Yang1, Liangyu Lin1, Guan Wang1, Pengfei Yu1, Xin Zhang1, Wei Cao1, Gary Brewer3, Ying Wang1 and Yufang Shi1,*

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 upregulated. 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.