STANDARD_NAME GSE40655_FOXO1_KO_VS_WT_NTREG_UP SYSTEMATIC_NAME M9439 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE40655_FOXO1_KO_VS_WT_NTREG_UP NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes up-regulated in normal T reg (nTreg): FOXO1 [GeneID=2308] versus wildtype. DESCRIPTION_FULL 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. PMID 23135404 GEOID GSE40655 AUTHORS Ouyang W,Liao W,Luo CT,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 CONTRIBUTOR Jernej Godec CONTRIBUTOR_ORG Dana-Farber Cancer Institute EXACT_SOURCE GSE40655_2890_200_UP FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ABHD8,ALG1,AP4E1,AR,ARHGAP1,ARHGAP5,ARHGEF12,ARID2,ASGR2,ATP13A1,ATP2B4,ATP8B1,AZI2,BBX,BCL11B,BIK,BOD1L,C1orf189,C2orf55,C2orf68,C8orf58,CAMK1D,CBX7,CCDC107,CD244,CELF1,CEP164,CHD3,CLN3,CNOT6L,COQ2,COQ5,CPSF1,CSK,CST3,CTCF,CTSW,DDX18,DDX39B,DDX46,DEXI,DMTF1,ELOVL7,EMG1,EXOSC1,FAM116B,FAM203A,FAM54B,FOXK1,FTH1,FTX,FYCO1,G3BP2,GAB3,GABBR1,GABRA2,GAPVD1,GGA3,GNA11,H2AFY,H6PD,HEATR1,HGSNAT,HIRA,HMHA1,HUWE1,IL16,IMP4,IRS1,KCTD12,KHNYN,KIAA0090,KIAA0100,KIAA0776,KIAA1109,KLHL26,KRI1,LAIR1,LGALS8,LHFPL5,LMBR1L,LPAR6,LY6E,MAST3,MAT2A,MBP,MEF2C,METTL17,MFAP1,MFSD6,MLL2,MLL3,MLL5,MLLT6,MLYCD,MMP9,MRPL47,MS4A7,MTCP1,MYCBP2,NAT10,NCOA6,NFIA,NOL9,NOLC1,NOP10,NPB,NTAN1,OLIG2,OSBPL7,OTUD4,PACS1,PAN2,PCNT,PCNXL3,PHF20L1,PHF3,PIK3CD,PITPNC1,PLEKHM3,PNPLA7,PPP1R12A,PPP2R5A,PPP6R3,PREX1,PRKACB,PRPF4B,PRPF8,PRPS1,PRRC2B,PTPN18,PWP2,PYGO2,RABEP2,RAI1,RAPGEF6,RASA3,RASSF5,RBM42,RELA,RNF123,RPL38,RRAD,SEC24C,SEPT6,SERPINB1,SGK1,SGSH,SLC12A5,SMPD1,SNAPC4,SNRNP70,SP1,SPNS1,ST3GAL6,SUN2,SZT2,TARS,TARS2,TAZ,TBX6,TCIRG1,TECPR1,THY1,TK2,TMEM64,TMEM91,TNK2,TOP2B,TOR1AIP1,TRAF3,TRIM39,TSPO,TTLL4,TUBA4A,TUG1,TULP4,UBL3,UBN1,UNK,USP48,USPL1,VEZF1,VPS28,WDR5,WDR82,ZBTB4,ZC3H11A,ZFC3H1,ZFP36L2,ZKSCAN1,ZMYM2,ZMYND11,ZNF146,ZNF182,ZNF187,ZNF287,ZNF490,ZNF770,ZNHIT2 GENE_SYMBOLS ABHD8,ALG1,AP4E1,AR,ARHGAP1,ARHGAP5,ARHGEF12,ARID2,ASGR2,ATP13A1,ATP2B4,ATP8B1,AZI2,BBX,BCL11B,BIK,BOD1L1,CFAP141,CRACDL,C2orf68,C8orf58,CAMK1D,CBX7,CCDC107,CD244,CELF1,CEP164,CHD3,CLN3,CNOT6L,COQ2,COQ5,CPSF1,CSK,CST3,CTCF,CTSW,DDX18,DDX39B,DDX46,DEXI,DMTF1,ELOVL7,EMG1,EXOSC1,DENND6B,HGH1,MTFR1L,FOXK1,FTH1,FTX,FYCO1,G3BP2,GAB3,GABBR1,GABRA2,GAPVD1,GGA3,GNA11,MACROH2A1,H6PD,HEATR1,HGSNAT,HIRA,ARHGAP45,HUWE1,IL16,IMP4,IRS1,KCTD12,KHNYN,EMC1,BLTP2,UFL1,BLTP1,KLHL26,KRI1,LAIR1,LGALS8,LHFPL5,LMBR1L,LPAR6,LY6E,MAST3,MAT2A,MBP,MEF2C,METTL17,MFAP1,MFSD6,KMT2D,KMT2C,KMT2E,MLLT6,MLYCD,MMP9,MRPL47,MS4A7,MTCP1,MYCBP2,NAT10,NCOA6,NFIA,NOL9,NOLC1,NOP10,NPB,NTAN1,OLIG2,OSBPL7,OTUD4,PACS1,PAN2,PCNT,PCNX3,PHF20L1,PHF3,PIK3CD,PITPNC1,PLEKHM3,PNPLA7,PPP1R12A,PPP2R5A,PPP6R3,PREX1,PRKACB,PRPF4B,PRPF8,PRPS1,PRRC2B,PTPN18,PWP2,PYGO2,RABEP2,RAI1,RAPGEF6,RASA3,RASSF5,RBM42,RELA,RNF123,RPL38,RRAD,SEC24C,SEPTIN6,SERPINB1,SGK1,SGSH,SLC12A5,SMPD1,SNAPC4,SNRNP70,SP1,SPNS1,ST3GAL6,SUN2,SZT2,TARS1,TARS2,TAFAZZIN,TBX6,TCIRG1,TECPR1,THY1,TK2,TMEM64,TMEM91,TNK2,TOP2B,TOR1AIP1,TRAF3,TRIM39,TSPO,TTLL4,TUBA4A,TUG1,TULP4,UBL3,UBN1,UNK,USP48,USPL1,VEZF1,VPS28,WDR5,WDR82,ZBTB4,ZC3H11A,ZFC3H1,ZFP36L2,ZKSCAN1,ZMYM2,ZMYND11,ZNF146,ZNF182,ZSCAN26,ZNF287,ZNF490,ZNF770,ZNHIT2 FOUNDER_NAMES