Abstract
The mechanism underlying T cell-mediated fulminant hepatitis is not fully understood. In this study, we investigated whether myeloid derived suppressor cells (MDSCs) could prevent the concanavalin A (ConA)-induced hepatitis through suppressing T cell proliferation. We observed an increase in the frequencies of MDSCs in mouse spleen and liver at early stage of ConA treatment, implicating that the MDSCs might be involved in the initial resistance of mice against ConA-mediated inflammation. Subpopulation analysis showed that the MDSCs in liver of ConA-induced mice were mainly granulocytic MDSCs. Adoptive transfer of the bone marrow-derived MDSCs into ConA-treated mice showed that the MDSCs migrated into the liver and spleen where they suppressed T cell proliferation through ROS pathway. In addition, the frequencies of MDSCs in mice were also significantly increased by the treatment with immune suppressor glucocorticoids. Transfer of MDSCs into the regulatory T cell (Treg)-depleted mice showed that the protective effect of MDSCs on ConA-induced hepatitis is Treg-independent. In conclusion, our results demonstrate that MDSCs possess a direct protective role in T cell-mediated hepatitis, and increasing the frequency of MDSCs by either adoptive transfer or glucocorticoid treatment represents a potential cell-based therapeutic strategy for the acute inflammatory disease.
Highlights
The mechanism underlying T cell-mediated fulminant hepatitis is not fully understood
Our results demonstrate that myeloid derived suppressor cells (MDSCs) possess a direct protective role in T cell-mediated hepatitis, and increasing the frequency of MDSCs by either adoptive transfer or glucocorticoid treatment represents a potential cell-based therapeutic strategy for the acute inflammatory disease
Displayed a significant lower level of serum TNF-α, IL-6, IL-12p70, and IFN-γ (Fig. 4G). These results implicate that the protection of DEX against concanavalin A (ConA)-induced hepatitis may be dependent on the induction of MDSCs
Summary
The mechanism underlying T cell-mediated fulminant hepatitis is not fully understood. Compared to mice treated with ConA alone, mice treated with ConA and DEX displayed a significant lower level of serum TNF-α, IL-6, IL-12p70, and IFN-γ (Fig. 4G) These results implicate that the protection of DEX against ConA-induced hepatitis may be dependent on the induction of MDSCs. Tregs have been reported as one of the cells targeted by MDSCs (Pan et al, 2008). The levels of AST and ALT (Fig. 5D) or TNF-α, IL-6, IL-12p70, and IFN-γ (Fig. 5E) were dramatically decreased in the serum of mice with BM-MDSCs transfer compared to those of mice without BM-MDSCs transfer These results implicate that MDSC can protect mouse liver from ConAmediated injury in a Treg-independent manner
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