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Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells.

CD4+ regulatory T cells (Tregs) maintain immunological self-tolerance and immune homeostasis by suppressing aberrant or excessive immune responses. The core genetic program of Tregs and their ability to suppress pathologic immune responses depends on the transcription factor Foxp3. Despite progress in understanding mechanisms of Foxp3-dependent gene activation, the molecular mechanism of Foxp3-dependent gene repression remains largely unknown. We identified Eos, a zinc-finger transcription factor of the Ikaros family, as a critical mediator of Foxp3-dependent gene silencing in Tregs. Eos interacts directly with Foxp3 and induces chromatin modifications that result in gene silencing in Tregs. Silencing of Eos in Tregs abrogates their ability to suppress immune responses and endows them with partial effector function, thus demonstrating the critical role that Eos plays in Treg programming.

Pubmed ID: 19696312


  • Pan F
  • Yu H
  • Dang EV
  • Barbi J
  • Pan X
  • Grosso JF
  • Jinasena D
  • Sharma SM
  • McCadden EM
  • Getnet D
  • Drake CG
  • Liu JO
  • Ostrowski MC
  • Pardoll DM


Science (New York, N.Y.)

Publication Data

August 28, 2009

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI058156
  • Agency: NIAID NIH HHS, Id: R01 AI058156-05
  • Agency: NIAID NIH HHS, Id: R01 AI089830

Mesh Terms

  • Acetylation
  • Alcohol Oxidoreductases
  • Animals
  • Carrier Proteins
  • Colitis
  • DNA Methylation
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Gene Knockdown Techniques
  • Gene Silencing
  • Histones
  • Humans
  • Interleukin-2
  • Jurkat Cells
  • Methylation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • RNA Interference
  • T-Lymphocytes, Regulatory
  • Transduction, Genetic
  • Zinc Fingers