Mesenchymal stem cells ameliorate experimental autoimmune hepatitis by activation of the programmed death 1 pathway.

Abstract

Previous studies have shown beneficial effects of mesenchymal stem cells (MSCs) transplantation in many autoimmune diseases. However, few studies have focused on the effects of MSCs on autoimmune hepatitis. In our study, we investigated the therapeutic effects of BMSCs (bone mesenchymal stem cells) transplantation in mouse experimental autoimmune hepatitis (EAH) and explored the potential mechanism. BMSCs were injected intravenously into EAH mice. Then, serum levels of ALT and AST, and pathologic alteration of liver tissue were measured to evaluate the liver function and inflammation degree. The expressions of programmed death ligand 1, IL-17 and IL-23 were detected by enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and western blotting. Upon serum biochemical levels and pathological examination, the BMSCs-treated mice especially with multiple dosing administration showed significantly reduction of liver damage. Moreover, the expression of IL-17 was down-regulated by BMSCs intervention as compared to the model group, whereas the PD-L1 and IL-23 were up-regulated following the administration of MSCs. In conclusion, the results of this study suggest that BMSCs transplantation, especially on multiple dosing, may exert immunosuppression effect to ameliorate EAH through the inhibition of IL-17 and up-regulation of PD-L1.

• Authors: Yi Chen, Si Chen, Li-Yuan Liu, Zhuo-Lin Zou, Yi-Jing Cai, Jin-Guo Wang, Bi Chen, Lan-Man Xu, Zhuo Lin, Xiao-Dong Wang, Yong-Ping Chen
• Journal: Immunology letters (Immunol Lett) Vol. 162 Issue 2 Pt B Pg. 222-8 (Dec 2014) ISSN: 1879-0542 [Electronic] Netherlands
• PMID: 25445618 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• B7-H1 Antigen
• Cd274 protein, mouse
• Interleukin-17
• Interleukin-23

Topics

• Animals
• B7-H1 Antigen (blood, immunology)
• Disease Models, Animal
• Gene Expression Regulation (immunology)
• Hepatitis, Autoimmune (blood, immunology, pathology, therapy)
• Interleukin-17 (blood, immunology)
• Interleukin-23 (blood, immunology)
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (immunology)
• Mice