Use of Epigenetic Modification to Induce FOXP3 Expression in Naïve T Cells

We investigated whether epigenetic modification agents can convert naïve T cells to regulatory T cells (Tregs) 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 Treg 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 Tregs induced by 5AzaD or TSA expressed greater amounts of the FOXP3 protein than the control and the natural Tregs. The analysis of Treg-associated markers also showed Treg phenotypes (CD25+/CTLA4+/GITR+/CD127−). Finally, the induced Treg 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 Tregs.