Interleukin-35 Gene-Modified Mesenchymal Stem Cells Protect Concanavalin A-Induced Fulminant Hepatitis by Decreasing the Interferon Gamma Level.

Abstract

Interleukin 35 (IL-35) is a relatively newly identified cytokine required for the regulatory and suppressive functions of regulatory T cells (Treg), playing an important role in the prevention of autoimmune diseases. This study used mesenchymal stem cells (MSCs) as the gene-delivery vehicles for IL-35 gene therapy and investigated their protective effects in Concanavalin A (Con A)-induced autoimmune hepatitis. Results showed that IL-35 gene modified MSCs (IL-35-MSCs) can specifically migrate to the injured liver tissues and significantly narrow the necrosis areas of injured livers. IL-35-MSCs prevented hepatocyte apoptosis by reducing the FASL expression by mononuclear cells. Although MSC treatment can alleviate liver injury to some extent, IL-35-MSCs showed a stronger protective effect, which means some novel mechanisms exist. The results show that IL-35-MSCs could decrease the level of interferon gamma secreted by liver mononuclear cells through the JAK1-STAT1/STAT4 signal pathway. In summary, this study thus demonstrates a novel and efficient treatment for Con A-induced fulminant hepatitis through negatively regulating the secretion of interferon gamma, thus providing a novel therapeutic approach for this devastating liver disease.

• Authors: Wei Wang, Hao Guo, Hongyue Li, Yongjia Yan, Chao Wu, Xiaodong Wang, Xianghui He, Na Zhao
• Journal: Human gene therapy (Hum Gene Ther) Vol. 29 Issue 2 Pg. 234-241 (02 2018) ISSN: 1557-7422 [Electronic] United States
• PMID: 29054137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FASLG protein, human
• Fas Ligand Protein
• Interleukins
• interleukin-35, human
• Concanavalin A
• Interferon-gamma
• Janus Kinase 1

Topics

• Animals
• Apoptosis (genetics)
• Concanavalin A (toxicity)
• Fas Ligand Protein
• Gene Expression Regulation (genetics)
• Gene Transfer Techniques
• Hepatitis, Autoimmune (etiology, genetics, therapy)
• Hepatocytes (metabolism, pathology)
• Humans
• Interferon-gamma (genetics)
• Interleukins (genetics, therapeutic use)
• Janus Kinase 1 (genetics)
• Liver (metabolism, pathology)
• Liver Failure, Acute (chemically induced, genetics, pathology, therapy)
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology)
• Mice
• T-Lymphocytes, Regulatory (metabolism, pathology)