期刊
HUMAN GENE THERAPY
卷 29, 期 2, 页码 234-241出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2017.171
关键词
interleukin-35; mesenchymal stem cells; liver injury; interferon gamma
资金
- National Natural Science Foundation of China for Young Scholars [31400764]
- Tianjin City High School Science and Technology Fund Planning Project [20130113]
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.
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