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Transplant Proc. 2009 Jun;41(5):1848-54. doi: 10.1016/j.transproceed.2009.02.101.

Use of epigenetic modification to induce FOXP3 expression in naïve T cells.

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  • 1Transplantation Research Center, Clinical Research Institute, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.


We investigated whether epigenetic modification agents can convert naïve T cells to regulatory T cells (T(regs)) which are responsible for limiting immune responses and maintaining self-tolerance. We treated splenic CD4(+)/CD25(-) naïve T cells from BALB/c mice with the DNA-methyltransferase inhibitor 5-aza-2'-deoxycytidine (5AzaD) or the histone protein deacetylase (HDAC) inhibitor Trichostatin A (TSA), and measured the effects on the expression of FOXP3, which encodes a transcription factor (FOXP3) that regulates T(reg) development. FOXP3 expression in naïve T cells was increased by 5AzaD or TSA treatment, administered 72 hours after T-cell receptor (TCR) stimulation with anti-CD3 plus anti-CD28. The T(regs) induced by 5AzaD or TSA expressed greater amounts of the FOXP3 protein than the control and the natural T(regs). The analysis of T(reg)-associated markers also showed T(reg) phenotypes (CD25(+)/CTLA4(+)/GITR(+)/CD127(-)). Finally, the induced T(reg) population also displayed T-cell suppression. These data suggested that epigenetic modification agents can induce FOXP3 expression, promoting the conversion of naïve T cells to T(regs).

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