SOCS1 Regulates the Immune Modulatory Properties of Mesenchymal Stem Cells by Inhibiting Nitric Oxide Production |
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| Authors: | Lei Zhang Rui-Jie Dang Hong Li Ping Li Yan-Mei Yang Xi-Min Guo Xiao-Yan Wang Nan-Zhu Fang Ning Mao Ning Wen Xiao-Xia Jiang |
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| Institution: | 1. Institute of Basic Medical Sciences, Beijing, China.; 2. Yanbian University, Yanji City, Jilin Province, China.; 3. Chinese PLA General Hospital, Beijing, China.; Josep Carreras Leukaemia Research Institute, University of Barcelona, Spain, |
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| Abstract: | Mesenchymal stem cells (MSCs) have been shown to be highly immunosuppressive and have been employed to treat various immune disorders. However, the mechanisms underlying the immunosuppressive capacity of MSCs are not fully understood. We found the suppressor of cytokine signaling 1 (SOCS1) was induced in MSCs treated with inflammatory cytokines. Knockdown of SOCS1 did not bring much difference on the proliferation and differentiation properties of MSCs. However, MSCs with SOCS1 knockdown exhibited enhanced immunosuppressive capacity, showing as inhibiting T cell proliferation at extremely low ratio (MSC to T) in vitro, significantly promoting tumor growth and inhibiting delayed-type hypersensitivity response in vivo. We further demonstrated that SOCS1 inhibited the immunosuppressive capacity of MSCs by reducing inducible nitric oxide synthase (iNOS) expression. Additionally, we found the significantly lower SOCS1 expression and higher nitric oxide (NO) production in MSCs isolated from synovial fluid of rheumatoid arthritis patients. Collectively, our data revealed a novel role of SOCS1 in regulating the immune modulatory activities of MSCs. |
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