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 (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).
Moon
C
C
Transplantation Research Center, Clinical Research Institute, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kim
S H
SH
Park
K S
KS
Choi
B K
BK
Lee
H S
HS
Park
J B
JB
Choi
G S
GS
Kwan
J H
JH
Joh
J W
JW
Kim
S J
SJ
D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine