Li Chichi, Sun Jian, Gong Yiming, Ding Xiaojun, Ruan Hong, Ye Lechi, Yu Youcheng
Zhongshan Hospital of Fudan University, Department of Stomatology , 180 Fenglin Road, Shanghai 200032, PR China +861 891 808 2340 ;
Expert Opin Biol Ther. 2014 May;14(5):573-81. doi: 10.1517/14712598.2014.896333. Epub 2014 Mar 11.
In a previous study, we showed that IFN-γ and TNF-α induce bone marrow mesenchymal stem cell (BMMSC) apoptosis and absorption of tissue-engineered cartilage, but the induced regulatory T cells (iTreg) inhibit the function of IFN-γ and TNF-α. In this study, we investigated the effect of iTreg cells on the absorption of tissue-engineered cartilage caused by endogenous IFN-γ and TNF-α.
We transfected the TGF-β1 gene into BMMSCs co-cultured with CD4(+) T lymphocytes. Then, we assessed the expression of iTreg cell markers (Foxp3, CD25 and CD 39) and IFN-γ and TNF-α and the level of apoptosis of BMMSCs. In addition, we characterized chondrogenic-committed cells from TGF-β1(+)BMMSCs and explored the role of iTreg cells.
IFN-γ and TNF-α were detected in the groups with CD4(+) T cells. In the group in which TGF-β1(+)BMMSCs were co-cultured with CD4(+) T cells, we observed Foxp3(+)Treg/ CD25(+)CD39(+) (17.58 ± 0.45%) cells as well as significant inhibition of BMMSC apoptosis and tissue-engineered cartilage absorption.
CD4(+) T cells led to the absorption of tissue-engineered cartilage through the secretion of endogenous IFN-γ and TNF-α, whose inflammatory functions were concomitantly suppressed by iTreg cells converted from CD4(+) T cells. This study is clinically relevant and adds to our understanding of the mechanism of tissue-engineered cartilage absorption.
在之前的一项研究中，我们发现干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）可诱导骨髓间充质干细胞（BMMSC）凋亡以及组织工程软骨吸收，但诱导调节性T细胞（iTreg）可抑制IFN-γ和TNF-α的功能。在本研究中，我们调查了iTreg细胞对内源性IFN-γ和TNF-α所致组织工程软骨吸收的影响。
我们将转化生长因子-β1（TGF-β1）基因转染至与CD4(+) T淋巴细胞共培养的BMMSC中。然后，我们评估了iTreg细胞标志物（叉头框蛋白3（Foxp3）、CD25和CD39）以及IFN-γ和TNF-α的表达情况和BMMSC的凋亡水平。此外，我们对来自TGF-β1(+)BMMSC的软骨定向分化细胞进行了鉴定，并探讨了iTreg细胞的作用。
在含有CD4(+) T细胞的组中检测到了IFN-γ和TNF-α。在TGF-β1(+)BMMSC与CD4(+) T细胞共培养的组中，我们观察到了Foxp3(+)调节性T细胞/CD25(+)CD39(+)（17.58±0.45%）细胞，同时BMMSC凋亡和组织工程软骨吸收受到显著抑制。
CD4(+) T细胞通过分泌内源性IFN-γ和TNF-α导致组织工程软骨吸收，而从CD4(+) T细胞转化而来的iTreg细胞可同时抑制其炎症功能。本研究具有临床相关性，增进了我们对组织工程软骨吸收机制的理解。
