A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells.
Relative upregulation of the Ikaros family transcription factor Helios in natural regulatory T cells (Tregs) has been reported by several groups. However, a role for Helios in regulatory T cells has not yet been described. Here, we show that Helios is upregulated in CD4(+)CD25(+) regulatory T cells. Chromatin-immunoprecipitation (ChIP) experiments indicated that Helios binds to the FoxP3 promoter. These data were further corroborated by experiments showing that knocking-down Helios with siRNA oligonucleotides results in down-regulation of FoxP3. Functionally, we found that suppression of Helios message in CD4(+)CD25(+) T cells significantly attenuates their suppressive function. Taken together, these data suggest that Helios may play an important role in regulatory T cell function and support the concept that Helios may be a novel target to manipulate Treg activity in a clinical setting.
Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.
Derese
D
Getnet
Joseph F
JF
Grosso
Monica V
MV
Goldberg
Timothy J
TJ
Harris
Hung-Rong
HR
Yen
Tullia C
TC
Bruno
Nicholas M
NM
Durham
Edward L
EL
Hipkiss
Kristin J
KJ
Pyle
Satoshi
S
Wada
Fan
F
Pan
Drew M
DM
Pardoll
Charles G
CG
Drake
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051379:Mice; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C111431:IKZF2 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D034741:RNA, Small Interfering; D014157:Transcription Factors; C491746:Zfpn1a2 protein, mouse; D051740:Ikaros Transcription Factor