title: 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.affiliation: Hepatology Institute of Wenzhou Medical University, Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hepatology Institute of Wenzhou Medical University, Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.affiliation: Hepatology Institute of Wenzhou Medical University, Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Liu
authors.affiliation: Hepatology Institute of Wenzhou Medical University, Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhuo-Lin
authors.initials: ZL
authors.lastname: Zou
authors.affiliation: Hepatology Institute of Wenzhou Medical University, Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: Cai
authors.affiliation: Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jin-Guo
authors.initials: JG
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Bi
authors.initials: B
authors.lastname: Chen
authors.affiliation: Hepatology Institute of Wenzhou Medical University, Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Lan-Man
authors.initials: LM
authors.lastname: Xu
authors.affiliation: Hepatology Institute of Wenzhou Medical University, Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Hepatology Institute of Wenzhou Medical University, Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Hepatology Institute of Wenzhou Medical University, Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: 13505777281@163.com.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Chen
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000097:blood / Q000276:immunology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D020381:Interleukin-17 / Q000097:blood / Q000276:immunology; D053759:Interleukin-23 / Q000097:blood / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23
keywords: Autoimmune hepatitis; Interleukin-17; Interleukin-23; Mesenchymal stem cells; Programmed death ligand 1