MicroRNA-155Alters Th1/Th2Proportion And Is Associated With Experimental Autoimmune Encephalomyelitis

Objective: To explore the effect of miR-155on the proportion of Th1and Th2cells in spleen and the concentration of IFN-γ, IL-4in the supernantof spleenocytes of mice with experimental autoimmune encephalomyelitis(EAE) and then make a basis for deeper investigation of the mechanisms,diagnosis and treatment of MS.Methods: Experimental autoimmune encephalomyelitis was induced infemale C57BL/6mice by immunization with MOGp35–55. The mice wererandomly divided into four groups:4mice in miR-155mimic group,4mice inmiR-155mimic control group,4mice in miR-155inhibitor group,4mice inmiR-155inhibitor control group. The drugs were administered in vivo to thesemice on days5,7,9, and11after immunization by intravenous injection. Theweight of mice and clinical symptoms were observed twice a day. All the micesacrificed to obtain the spleens on day20(fastigium duration). The proportionof Th1and Th2cells in spleens was tested by Flow Cytometry. The concentra-tion of IFN-γ, IL-4and IL-10in the supernant of spleenocytes was observedby ELISA respectively. Additionally, the levels of IFN-γ mRNA, IL-4mRNAand IL-10mRNA in spleen cells of the groups above were measured by RT-PCR.Results:1Compared to miR-155mimic control group, the morbidity、weight lossand mean clinical scores of mice in miR-155mimic group on Day20weresignificantly higher (P<0.05). Compared to miR-155inhibitor control group,the morbidity、weight loss and mean clinical scores of mice in miR-155inhibitor group were significantly lower (P<0.05).2The proportion of Th1and Th2in the spleen of mice in five groups:comparing to control group, Th1cells was significantly increased and Th2 cells was decreased in miR-155mimic group (P<0.05); comparing to controlgroup, Th1cells was significantly decreased and Th2cells was increased inmiR-155inhibitor group (P<0.05).3The concentration of IFN-γ，IL-4and IL-10in the supernatant ofspleenocytes in five groups: comparing to control group, the concentration ofIFN-γ was significantly increased and IL-4and IL-10were decreased in miR-155mimic group (P<0.05); comparing to control group, the concentration ofIFN-γ was decreased significantly and IL-4and IL-10were increased in miR-155inhibitor group (P<0.05).4The level of IFN-γ mRNA,IL-4mRNA and IL-10mRNA in the spleencells in five groups: comparing to control group, the level of IFN-γ mRNAwas significantly increased and IL-4mRNA and IL-10mRNA were decreasedin miR-155mimic group (P<0.05); comparing to control group, the level ofIFN-γ mRNA was decreased significantly and IL-4mRNA and IL-10mRNAwere increased in miR-155inhibitor group (P<0.05).Conclusions:1MiR-155could influence the morbidity of EAE, the onset time andthe clinical scores.2MiR-155could decrease the expression of IL-4and IL-10and increasethe expression of IFN-γ, upregulate the proportion of Th1cells, as well asdownregulate the proportion of Th2cells at the same time in the spleen ofmice. MiR-155effects EAE through these immune-modulated ways above.