Transforming growth factor-β1-induced Treg cells inhibit the absorption of tissue-engineered cartilage caused by endogenous IFN-γ and TNF-α

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords::

• bone marrow mesenchymal stem cells
• CD4⁺ T cells
• chondrocytes
• transforming growth factor-β1

Acknowledgment

Chichi Li and Sun Jian contributed equally to this work.

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