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.
Pan
Fan
F
Immunology and Hematopoiesis Division, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Yu
Hong
H
Dang
Eric V
EV
Barbi
Joseph
J
Pan
Xiaoyu
X
Grosso
Joseph F
JF
Jinasena
Dinili
D
Sharma
Sudarshana M
SM
McCadden
Erin M
EM
Getnet
Derese
D
Drake
Charles G
CG
Liu
Jun O
JO
Ostrowski
Michael C
MC
Pardoll
Drew M
DM
D000107:Acetylation; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003092:Colitis / Q000276:immunology; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D019169:Jurkat Cells; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*; D014161:Transduction, Genetic; D016335:Zinc Fingers
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006657:Histones; D007376:Interleukin-2; D009419:Nerve Tissue Proteins; C118760:Zfpn1a4 protein, mouse; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein
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