MicroRNA let-7a Ameliorates Con A-Induced Hepatitis by Inhibiting IL-6-Dependent Th17 Cell Differentiation

In this study we explored the effects of microRNA let-7a on Con A-induced hepatitis and its possible mechanisms involved. We demonstrated that IL-6 and IL-17 expression were significantly upregulated in the liver following Con A treatment and IL-6 level was correlated with the IL-17 expression. To explore whether let-7a may have therapeutic effect on Con A-induced hepatitis, mice was infected with a lentiviral vector containing the let-7a sequence 7 days before Con A treatment. Significantly reduced Th17 cells and remarkably increased regulatory T cells frequency in the liver tissue were found as compared to control mice. It was accompanied by a significant decreased level of inflammatory cytokines as TNF-α, IL-6 and IFN-γ in the serum, and an decreased level of Th17 lineage-specific genes such as Il17a, Il17f, Il21 and Il23r. let-7a was further found to inhibit Th17 differentiation by downregulating IL-6 secretion. It may represent as a novel therapeutic strategy in treating immune-mediated inflammatory hepatitis.