Liu Yi, Yin Zhilin, Zhang Run, Yan Ke, Chen Lei, Chen Fanfan, Huang Weiyi, Lv Bingke, Sun Chengmei, Jiang Xiaodan
The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Biochem Biophys Res Commun. 2014 Aug 8;450(4):1409-15. doi: 10.1016/j.bbrc.2014.07.001. Epub 2014 Jul 8.
Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that are characterized by the ability to take up and process antigens and prime T cell responses. Mesenchymal stem cells (MSCs) are multipotent cells that have been shown to have immunomodulatory abilities, including inhibition of DC maturation and function in vivo and in vitro; however, the underlying mechanism is far from clear. In this study we found that MSCs can inhibit the maturation and function of bone marrow-derived DCs by releasing TSG-6. In the presence of MSCs, lower expression of mature DC surface phenotype (CD80, CD86, MHC-II, and CD11c) was observed. In addition, typical DC functions, such as the production of IL-12 and the ability to prime T cells, were decreased when co-cultured with MSCs. In contrast, knockdown of TSG-6 reduced the inhibitory effect of MSCs on DC. Moreover, we found that TSG-6 can suppress the activation of MAPKs, and NF-κB signaling pathways within DCs during Lipopolysaccharides (LPS) stimulation. In conclusion, we suggest that TSG-6 plays an important role in MSCs-mediated immunosuppressive effect on DC.
树突状细胞（DCs）是强大的抗原呈递细胞（APCs），其特征在于具有摄取和处理抗原以及启动T细胞反应的能力。间充质干细胞（MSCs）是多能细胞，已显示具有免疫调节能力，包括在体内和体外抑制DC成熟和功能；然而，其潜在机制尚不清楚。在本研究中，我们发现MSCs可通过释放TSG-6抑制骨髓来源的DC成熟和功能。在存在MSCs的情况下，观察到成熟DC表面表型（CD80、CD86、MHC-II和CD11c）的表达降低。此外，当与MSCs共培养时，典型的DC功能，如IL-12的产生和启动T细胞的能力降低。相反，TSG-6的敲低降低了MSCs对DC的抑制作用。此外，我们发现TSG-6可在脂多糖（LPS）刺激期间抑制DC内MAPKs和NF-κB信号通路的激活。总之，我们认为TSG-6在MSCs介导的对DC的免疫抑制作用中起重要作用。
