title: miR-155 regulates immune modulatory properties of mesenchymal stem cells by targeting TAK1-binding protein 2.
abstract: 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.
authors: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, 225 South Chongqing Road, Shanghai 200025, China.
authors: Chunliang
authors: C
authors: Xu
authors: Guangwen
authors: G
authors: Ren
authors: Gang
authors: G
authors: Cao
authors: Qing
authors: Q
authors: Chen
authors: Peishun
authors: P
authors: Shou
authors: Chunxing
authors: C
authors: Zheng
authors: Liming
authors: L
authors: Du
authors: Xiaoyan
authors: X
authors: Han
authors: Menghui
authors: M
authors: Jiang
authors: Qian
authors: Q
authors: Yang
authors: Liangyu
authors: L
authors: Lin
authors: Guan
authors: G
authors: Wang
authors: Pengfei
authors: P
authors: Yu
authors: Xin
authors: X
authors: Zhang
authors: Wei
authors: W
authors: Cao
authors: Gary
authors: G
authors: Brewer
authors: Ying
authors: Y
authors: Wang
authors: Yufang
authors: Y
authors: Shi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000276:immunology*; D055785:Gene Knockdown Techniques; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053583:Interleukin-1beta; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; C498761:Tab2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse