A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells

Mol Immunol. 2010 Apr;47(7-8):1595-600. doi: 10.1016/j.molimm.2010.02.001. Epub 2010 Mar 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Down-Regulation
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Humans
  • Ikaros Transcription Factor / genetics
  • Ikaros Transcription Factor / immunology*
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Mice
  • Promoter Regions, Genetic
  • RNA, Small Interfering / genetics
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • Up-Regulation

Substances

  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IKZF2 protein, human
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • RNA, Small Interfering
  • Transcription Factors
  • Zfpn1a2 protein, mouse
  • Ikaros Transcription Factor