Researchers from the Key Laboratory of Stem Cell Biology, Shanghai Institute of Biochemistry, Chinese Academy of Sciences, and the New Jersey Institute of Children ’s Health published an article entitled "MiR-155 Regulates Immune Modulatory Properties of Mesenchymal Stem Cells by Targeting TAK1-binding Protein 2". A small RNA called miR-155 can reduce the expression of iNOSitol by targeting TABs, thereby regulating the immune regulation ability of MSCs, thus revealing the new role of miR-155. Related results were published in JBC Magazine. The corresponding author of the article is Shi Yufang, a researcher at the Chinese Academy of Sciences, Shanghai Academy of Sciences. Shi Yufang is a discoverer of activation-induced lymphocyte death and c-myc on T cell apoptosis. The relationship between death and stress response or immunosuppression caused by opium has proved the decisive role of CD4 + T cells in asthma, and has proposed a new direction for the treatment of allergic asthma. Recently it was hired as a journal of Nature Press: Cell One of the editors in chief of Death & Disease.
Mesenchymal stem cells (MSCs) are a type of tissue stem cells with multi-directional differentiation potential that are widely present in the body. They are also valued for their important immunomodulatory effects. In recent years, they have been used in animal models and clinical studies of disease models. MSCs have been tried to treat immune disorders. Although many articles have reported that MSCs have very good therapeutic effects, their treatment indications, timing of diagnosis and treatment, and mechanism of action need to be further studied. Previously, Shi Yufang and others have found that the immune regulation of mesenchymal stem cells (MSCs) is affected by the inflammatory response state and the amount of nitric oxide / IDO produced, and this effect is through the inflammatory factors IFNγ, TNFα and IL-1β Co-induced. Since these inflammatory factors have a great influence on MSCs, with the expression of iNOSitol and chemokines, they increase logarithmically, so it is very important to understand the specific mechanism of action.
To this end, in this latest study, the researchers conducted an in-depth discussion. In order to analyze the molecular mechanism behind the huge impact of these cytokines, they insisted on the expression of small molecule RNA (miRNAs) in MSCs before and after cytokine administration. . The results showed that the expression of a small molecule RNA called miR-155 increased significantly, and this study also showed that miR-155 can inhibit the immunosuppressive capacity of bone marrow mesenchymal stem cells, which is achieved by reducing the expression of iNOSitol.
Through further research, the researchers also found that miR-155 can target TAK1 binding protein 2 (TAB2) and regulate the expression of iNOS. If TAB2 is knocked out, it will reduce the expression of iNOS. Therefore, this study shows that miR-155 can reduce the expression of iNOSitol by targeting TABs, thereby inhibiting the immunosuppressive capacity of MSCs. This reveals the new role of miR-155: regulating the immune regulation of bone marrow mesenchymal stem cells. Previous work by Shi Yufang's research group has found that MSCs can secrete a large amount of chemokines and immunosuppressive nitric oxide or indole 2,3-dioxygenase (IDO) under the stimulation of inflammatory factors. Under the action of chemokines, immune cells are chemoattracted around MSCs and inhibited by their local high concentration of nitric oxide or tryptophan deficiency caused by IDO. As a result, the research team conducted a series of studies and found that the immune regulation of mesenchymal stem cells (MSCs) was affected by the state of inflammation and the amount of nitric oxide / IDO produced, which also laid the foundation for this research. .
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