title: 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.
authors.affiliation: Zhongshan Hospital of Fudan University, Department of Stomatology , 180 Fenglin Road, Shanghai 200032, PR China +861 891 808 2340 ; 2003130823@163.com.
authors.forename: Chichi
authors.initials: C
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Yiming
authors.initials: Y
authors.lastname: Gong
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ding
authors.forename: Hong
authors.initials: H
authors.lastname: Ruan
authors.forename: Lechi
authors.initials: L
authors.lastname: Ye
authors.forename: Youcheng
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002356:Cartilage / Q000378:metabolism*; D018920:Coculture Techniques; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023822:Tissue Engineering; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma