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Series GSE40655 Query DataSets for GSE40655
Status Public on Sep 07, 2012
Title Novel Foxo1-dependent Transcriptional Programs Control Treg Cell Function [Affymetrix gene expression data]
Organism Mus musculus
Experiment type Expression profiling by array
Summary Regulatory T (Treg) cells characterized by expression of the transcription factor forkhead box P3 (Foxp3) maintain immune homeostasis by suppressing self-destructive immune responses1-4. Foxp3 operates as a late acting differentiation factor controlling Treg cell homeostasis and function5, whereas the early Treg cell lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors6-10. However, whether Foxo proteins act beyond the Treg cell commitment stage to control Treg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of Treg cell function. Treg cells express high amounts of Foxo1, and display reduced T-cell receptor-induced Akt activation, Foxo1 phosphorylation, and Foxo1 nuclear exclusion. Mice with Treg cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to Foxp3-deficient mice, but without the loss of Treg cells. Genome-wide analysis of Foxo1 binding sites reveals ~300 Foxo1-bound target genes, including the proinflammatory cytokine Ifng, that do not appear to be directly regulated by Foxp3. These findings demonstrate that the evolutionarily ancient Akt-Foxo1 signaling module controls a novel genetic program indispensable for Treg cell function.
 
Overall design Regulatory T cells were FACS sorted in WT mice (2 reps), Foxo1 KO mice (2 reps), mice expressing a constitutively active form of Foxo1 (1 rep), and Foxo1 KO mice expressing constitutively active Foxo1. We identified genes differentially expressed in WT vs. KO mice and assessed whether expression was recovered in the KO in presence of constitutively active Foxo1
 
Contributor(s) Ouyang W, Liao W, Luo C, Yin N, Huse M, Kim MV, Peng M, Chan P, Ma Q, Mo Y, Meijer D, Zhao K, Rudensky AY, Atwal G, Zhang MQ, Li MO
Citation(s) 23135404
Submission date Sep 06, 2012
Last update date Feb 11, 2019
Contact name Willey Liao
Organization name New York Genome Center
Department Bioinformatics
Street address 101 Avenue of the Americas
City New York
State/province NY
ZIP/Postal code 10013
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (6)
GSM998918 nTreg Foxo1 KO, Constitutively Active Foxo1
GSM998919 nTreg, Constitutively Active Foxo1
GSM998920 nTreg Foxo1 KO, rep1
This SubSeries is part of SuperSeries:
GSE40657 Novel Foxo1-dependent Transcriptional Programs Control Treg Cell Function
Relations
BioProject PRJNA174585

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE40655_RAW.tar 22.4 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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