Document Detail


A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells.
MedLine Citation:
PMID:  20226531     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Derese Getnet; Joseph F Grosso; Monica V Goldberg; Timothy J Harris; Hung-Rong Yen; Tullia C Bruno; Nicholas M Durham; Edward L Hipkiss; Kristin J Pyle; Satoshi Wada; Fan Pan; Drew M Pardoll; Charles G Drake
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-03-11
Journal Detail:
Title:  Molecular immunology     Volume:  47     ISSN:  1872-9142     ISO Abbreviation:  Mol. Immunol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-05     Completed Date:  2010-04-22     Revised Date:  2014-01-16    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1595-600     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
CD4-Positive T-Lymphocytes / cytology,  immunology*
Cell Line
DNA-Binding Proteins / genetics,  immunology*
Down-Regulation
Forkhead Transcription Factors / genetics,  immunology
Humans
Ikaros Transcription Factor / genetics,  immunology*
Interleukin-2 Receptor alpha Subunit / immunology
Mice
Promoter Regions, Genetic
RNA, Small Interfering / genetics
Transcription Factors / genetics,  immunology*
Up-Regulation
Grant Support
ID/Acronym/Agency:
K08 CA096948/CA/NCI NIH HHS; K08 CA096948/CA/NCI NIH HHS; K08 CA096948-05/CA/NCI NIH HHS; R01 CA127153/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/IKZF2 protein, human; 0/IL2RA protein, human; 0/Interleukin-2 Receptor alpha Subunit; 0/RNA, Small Interfering; 0/Transcription Factors; 0/Zfpn1a2 protein, mouse; 148971-36-2/Ikaros Transcription Factor
Comments/Corrections

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