Zhang Lei, Dang Rui-Jie, Li Hong, Li Ping, Yang Yan-Mei, Guo Xi-Min, Wang Xiao-Yan, Fang Nan-Zhu, Mao Ning, Wen Ning, Jiang Xiao-Xia
Institute of Basic Medical Sciences, Beijing, China; Yanbian University, Yanji City, Jilin Province, China.
Chinese PLA General Hospital, Beijing, China.
PLoS One. 2014 May 14;9(5):e97256. doi: 10.1371/journal.pone.0097256. eCollection 2014.
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.
间充质干细胞（MSCs）已被证明具有高度免疫抑制作用，并已被用于治疗各种免疫疾病。然而，MSCs免疫抑制能力的潜在机制尚未完全了解。我们发现，在用炎性细胞因子处理的MSCs中，细胞因子信号传导抑制因子1（SOCS1）被诱导。敲低SOCS1对MSCs的增殖和分化特性没有太大影响。然而，敲低SOCS1的MSCs表现出增强的免疫抑制能力，表现为在体外以极低的比例（MSC与T细胞的比例）抑制T细胞增殖，在体内显著促进肿瘤生长并抑制迟发型超敏反应。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出的MSCs中，SOCS1表达明显降低，一氧化氮（NO）产生增加。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。
