SOCS1 regulates the immune modulatory properties of mesenchymal stem cells by inhibiting nitric oxide production.

SOCS1 regulates the immune modulatory properties of mesenchymal stem cells by inhibiting nitric oxide production.
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SOCS1 通过抑制一氧化氮的产生来调节间充质干细胞的免疫调节特性

DOI:
10.1371/journal.pone.0097256
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Jiang XX
Jiang XX
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang L;Dang RJ;Li H;Li P;Yang YM;Guo XM;Wang XY;Fang NZ;Mao N;Wen N;Jiang XX

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间充质干细胞(MSCs)已被证明具有高度的免疫抑制作用,并已被用于治疗各种免疫疾病。然而,MSCs免疫抑制能力的机制尚不完全清楚。我们发现细胞因子信号1的抑制因子(SOCS1)在炎症细胞因子处理的间充质干细胞中被诱导。SOCS1基因的敲低对MSCs的增殖和分化特性没有太大影响。然而,SOCS1敲低的MSCs表现出增强的免疫抑制能力,在体外以极低比例(MSC / T)抑制T细胞增殖,在体内显著促进肿瘤生长,抑制延迟型超敏反应。我们进一步证明,SOCS1通过降低诱导型一氧化氮合酶(iNOS)的表达来抑制MSCs的免疫抑制能力。此外,我们发现从类风湿性关节炎患者滑液中分离的MSCs中SOCS1的表达显著降低,一氧化氮(NO)的产生显著增加。总的来说,我们的数据揭示了SOCS1在调节MSCs免疫调节活性中的新作用。
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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