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

Author:

Pan Fan1,Yu Hong1,Dang Eric V.1,Barbi Joseph1,Pan Xiaoyu1,Grosso Joseph F.1,Jinasena Dinili1,Sharma Sudarshana M.2,McCadden Erin M.1,Getnet Derese1,Drake Charles G.1,Liu Jun O.3,Ostrowski Michael C.2,Pardoll Drew M.1

Affiliation:

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.

Abstract

T reg Responses to Eos CD4 + regulatory T cells (T regs ) are critical for keeping our immune system in check: They prevent immune responses from getting out of hand and keep autoimmunity at bay. By activating the expression of some genes and turning off expression of others, the master regulatory transcription factor of T regs , Foxp3, endows these cells with the appropriate gene expression program to mediate their suppressive effects. Pan et al. (p. 1142 , published online 20 August) now demonstrate that the transcription factor Eos is selectively required for Foxp3-mediated gene suppression in mice. Genes normally suppressed by Foxp3 in T regs remained “on” when Eos expression was suppressed, whereas genes activated by Foxp3 were unaffected. T reg function was also affected by Eos suppression. With half their genetic program disrupted, these cells resembled an intermediate between T regs and conventional CD4 + T cells—unable to suppress immune responses properly and partially responsive to T cell–activating stimulation.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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