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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / genetics
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Cell Line
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Cell Proliferation / genetics
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Cytokines / genetics
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Cytokines / metabolism
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Humans
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Immunologic Factors / genetics
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Immunologic Factors / metabolism*
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Immunosuppression Therapy / methods
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Mesenchymal Stem Cells / metabolism*
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Mice
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Mice, Inbred C57BL
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Nitric Oxide / metabolism*
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Suppressor of Cytokine Signaling Proteins / genetics
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Suppressor of Cytokine Signaling Proteins / metabolism*
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T-Lymphocytes / metabolism
Substances
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Cytokines
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Immunologic Factors
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Intracellular Signaling Peptides and Proteins
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Suppressor of Cytokine Signaling Proteins
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Nitric Oxide
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Nitric Oxide Synthase Type II
Grants and funding
This study was supported by grants from the National Natural Science Foundation of China (81271936, 81070393, 81170523, 81170461, 31170926), the Chinese National Key Program on Basic Research(2010CB529904)and the National High-Tech Research and Development Program (2011AA020114). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.