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Science 325 (5944): 1142-1146

Copyright © 2009 by the American Association for the Advancement of Science

Eos Mediates Foxp3-Dependent Gene Silencing in CD4+ Regulatory T Cells

Fan Pan,1 Hong Yu,1 Eric V. Dang,1 Joseph Barbi,1 Xiaoyu Pan,1 Joseph F. Grosso,1 Dinili Jinasena,1 Sudarshana M. Sharma,2 Erin M. McCadden,1 Derese Getnet,1 Charles G. Drake,1 Jun O. Liu,3 Michael C. Ostrowski,2 Drew M. Pardoll1,*

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 Treg programming.

1 Immunology and Hematopoiesis Division, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
2 Department of Molecular and Cellular Biochemistry and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
3 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

* To whom correspondence should be addressed. E-mail: dpardol1{at}jhmi.edu


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