Mitochondrial biogenesis is essential in adipocyte differentiation

antimiR-155. In the contrast, the mRNA levels of GATA-binding protein-3 and IL-4 were down-Piclidenoson web regulated by pre-miR155 and up-regulated by anti-miR-155. These results show that miR-155 induces the differentiation and function of Th1 cell and inhibits the differentiation and function of Th2 cell. MiR-155 regulates the expression of T-bet/GATA-3 and IFN-c/IL-4 in the development of Th1/Th2 cells Discussion We have shown here that miR-155 is a critical player in driving Treg/Th17 cells differentiation and enhancing Th17 cell function by directly inhibiting SOCS1. SOCS1 is a negative regulator of Janus kinase /STAT signaling pathway. Recently, the effect of SOCS1 on the development of Treg/Th17 cells has been MicroRNA-155 and Treg/Th17 Cells studied. Lu et al. and Zhan et al. found that T-cellspecific deletion of SOCS1 resulted in an increase in the proportion and absolute numbers of Treg cells in the thymus. But it was not found that SOCS1 negatively regulated the suppressive function of Treg cells. The role of SOCS1 in Th17 cell differentiation and function was clarified by Johnson and his group by characterizing a mimetic of SOCS1, namely novel tyrosine kinase inhibitor peptide. They found that Tkip blocked IL6-induced activation of STAT3, inhibited the development of Th17 and the production of IL-17A. As a result, the development of EAE in both acute and chronic phases was prevented by Tkip. So, the differentiation of Treg and Th17 cells and the production of IL-17A were increased when the expression of SOCS1 was inhibited by miR-155. Treg and Th17 cells are induced from uncommitted CD4+ T cells by different cytokine-driven signaling pathways. IL-6/STAT3 is indispensable for Th17 cells differentiation, and inhibits Treg cells. Conditional deletion of STAT3 in CD4+ T cells impairs Th17 differentiation, IL-17A production, and limits EAE development. Conversely, IL-2/STAT5 is essential for mainte- 3 MicroRNA-155 and Treg/Th17 Cells nance of homeostasis and competitive fitness of Treg cells, and suppresses Th17 differentiation. However, Fontenot et al. found that the function of IL-22/2 and IL-2ra2/2 Treg cells was equivalent to that of wild-type Treg cells, which indicated that IL-2/STAT5 signaling pathway was dispensable for Treg cell function. In the present study, we found that miR-155 positively regulated STAT5 and STAT3 phosphorylations. This must because miR-155 blocked the SOCS1-mediated inhibitory effect on STAT5 and STAT3 phosphorylations. TGF-b1 is essential for both Treg and Th17 cells differentiation. It induces Foxp3 expression and promotes Treg cell function by activating SMAD5 signaling pathway. It also works together with IL-6 to induce Th17 differentiation by activating SMAD2 signaling pathway. Both SMAD5 and SMAD2 were validated to be targets of miR-155 in different papers. Louafi et al. demonstrated that miR-155 modulated the response of macrophage to TGF-b1 by targeting SMAD2. While SMAD5 was found to be directly inhibited by miR-155 in B cell lymphoma cells. But, in our study, neither the phosphorylations of SMAD5/ SMAD2 nor the expression of the total proteins were regulated by miR-155 in CD4+ T cells, although phosphorylation of SMAD2 and the total proteins were down-regulated in RAW264.7 cells when miR-155 was over-expressed. This might because miR-155 prone to inhibit different transcripts in a cell-specific manner and SMAD2 was inhibited by miR-155 in macrophage and macrophage cell lines but not in T lymphocytes. Usin