The protective role of myeloid-derived suppressor cells in concanavalin A-induced hepatic injury

• Published in: Protein & cell 2014-09, Vol.5 (9), p.714-724
• Main Authors: Diao, Wenli, Jin, Fangfang, Wang, Bing, Zhang, Chen-Yu, Chen, Jiangning, Zen, Ke, Li, Limin
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Biochemistry; Biomedical and Life Sciences; Blotting, Western; Bone Marrow Cells - immunology; CD11b Antigen - immunology; CD11b Antigen - metabolism; Cell Biology; Cell Movement - immunology; Cell Proliferation; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - immunology; Chemical and Drug Induced Liver Injury - prevention & control; concanavalin A (ConA); Concanavalin A - toxicity; Developmental Biology; Dexamethasone - pharmacology; Flow Cytometry; glucocorticoid treatment; glucocorticoids; Glucocorticoids - pharmacology; Human Genetics; Life Sciences; Liver - immunology; Liver - pathology; Male; Mice, Inbred C57BL; Mitogens - administration & dosage; Mitogens - toxicity; Myeloid Cells - immunology; Myeloid Cells - metabolism; Myeloid Cells - transplantation; myeloid derived suppressor cells; Protein Science; Receptors, Chemokine - immunology; Receptors, Chemokine - metabolism; Research Article; ROS; Spleen - immunology; Spleen - pathology; Stem Cells; T cellmediated hepatitis; T-Lymphocytes - immunology; T-Lymphocytes, Regulatory - immunology; T细胞增殖; 伴刀豆球蛋白A; 保护作用; 激素治疗; 糖皮质激素; 肝损伤; 诱导; 调节性T细胞
• ISSN: 1674-800X; 1674-8018
• DOI: 10.1007/s13238-014-0069-5

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.