MSCs inhibit bone marrow-derived DC maturation and function through the release of TSG-6

作者:Liu, Yi; Yin, Zhilin; Zhang, Run; Yan, Ke; Chen, Lei; Chen, Fanfan; Huang, Weiyi; Lv, Bingke; Sun, Chengmei; Jiang, Xiaodan*
来源:Biochemical and Biophysical Research Communications, 2014, 450(4): 1409-1415.
DOI:10.1016/j.bbrc.2014.07.001

摘要

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-kappa B 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.