Eos mediates foxp3-dependent gene silencing in CD4+ regulatory T cells

Fan Pan, Hong Yu, Eric V. Dang, Joseph Barbi, Xiaoyu Pan, Joseph F. Grosso, Dinili Jinasena, Sudarshana M. Sharma, Erin M. McCadden, Derese Getnet, Charles G. Drake, Jun Liu, Michael C. Ostrowski, Andrew Mark Pardoll

Research output: Contribution to journalArticle

Abstract

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 Tregs programming.

Original languageEnglish (US)
Pages (from-to)1142-1146
Number of pages5
JournalScience
Volume325
Issue number5944
DOIs
StatePublished - 2009

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Gene Silencing
Regulatory T-Lymphocytes
Ikaros Transcription Factor
Self Tolerance
Zinc Fingers
Transcriptional Activation
Chromatin
Homeostasis
Transcription Factors
Genes

ASJC Scopus subject areas

  • General

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Eos mediates foxp3-dependent gene silencing in CD4+ regulatory T cells. / Pan, Fan; Yu, Hong; Dang, Eric V.; Barbi, Joseph; Pan, Xiaoyu; Grosso, Joseph F.; Jinasena, Dinili; Sharma, Sudarshana M.; McCadden, Erin M.; Getnet, Derese; Drake, Charles G.; Liu, Jun; Ostrowski, Michael C.; Pardoll, Andrew Mark.

In: Science, Vol. 325, No. 5944, 2009, p. 1142-1146.

Research output: Contribution to journalArticle

Pan, F, Yu, H, Dang, EV, Barbi, J, Pan, X, Grosso, JF, Jinasena, D, Sharma, SM, McCadden, EM, Getnet, D, Drake, CG, Liu, J, Ostrowski, MC & Pardoll, AM 2009, 'Eos mediates foxp3-dependent gene silencing in CD4+ regulatory T cells', Science, vol. 325, no. 5944, pp. 1142-1146. https://doi.org/10.1126/science.1176077
Pan, Fan ; Yu, Hong ; Dang, Eric V. ; Barbi, Joseph ; Pan, Xiaoyu ; Grosso, Joseph F. ; Jinasena, Dinili ; Sharma, Sudarshana M. ; McCadden, Erin M. ; Getnet, Derese ; Drake, Charles G. ; Liu, Jun ; Ostrowski, Michael C. ; Pardoll, Andrew Mark. / Eos mediates foxp3-dependent gene silencing in CD4+ regulatory T cells. In: Science. 2009 ; Vol. 325, No. 5944. pp. 1142-1146.
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abstract = "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 Tregs programming.",
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AU - Grosso, Joseph F.

AU - Jinasena, Dinili

AU - Sharma, Sudarshana M.

AU - McCadden, Erin M.

AU - Getnet, Derese

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AU - Liu, Jun

AU - Ostrowski, Michael C.

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