STANDARD_NAME GSE23505_UNTREATED_VS_4DAY_IL6_IL1_TREATED_CD4_TCELL_DN SYSTEMATIC_NAME M7863 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE23505_UNTREATED_VS_4DAY_IL6_IL1_TREATED_CD4_TCELL_DN NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes down-regulated in CD4 [GeneID=920] T cells: untreated versus IL1B and IL6 [GeneID=3553;3569]. DESCRIPTION_FULL CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification7-10. Herein, we show that Th17 differentiation occurs in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-β1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies. PMID 20962846 GEOID GSE23505 AUTHORS Ghoreschi K,Laurence A,Yang XP,Tato CM,McGeachy MJ,Konkel JE,Ramos HL,Wei L,Davidson TS,Bouladoux N,Grainger JR,Chen Q,Kanno Y,Watford WT,Sun HW,Eberl G,Shevach EM,Belkaid Y,Cua DJ,Chen W,O'Shea JJ CONTRIBUTOR Jernej Godec CONTRIBUTOR_ORG Dana-Farber Cancer Institute EXACT_SOURCE GSE23505_2884_200_DN FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ACHE,ACTL7A,ADAM9,ALB,AMFR,ANKH,ANXA1,AP3S1,APEX1,ARHGAP24,ATP11B,ATP1B3,BARHL1,BCS1L,BEST2,BEX1,BIRC2,BLCAP,BNIPL,BST1,C10orf118,C12orf29,C19orf21,C3,C4orf29,CCDC88A,CCL19,CD2AP,CDH11,CDKN1A,CELSR3,CFB,CHD1L,CHST4,CLDN19,CLDN6,CLEC5A,COCH,COMMD9,CRIP3,CRTAP,CSF2RB,CSN2,CSN3,CTNNB1,CYTH3,DCLK1,DEPTOR,DERL1,DGUOK,DHX9,DIO1,DSC3,DTX1,EEPD1,EHD3,ENPP2,ESRRB,EXOSC4,EXTL1,FABP4,FADS2,FAM134A,FAM13B,FAM184B,FAM190B,FAM3D,FBP2,FCAMR,FNDC7,GBA,GDA,GGPS1,GJA1,GLP1R,GPX6,GSR,GSTA3,GSTM1,GTF2IRD1,HAS2,HES3,HIATL1,HOMER2,HSPA14,IGF1R,IL20,IL7R,ITIH5,KCNA3,KCND3,KIAA1199,KIAA1704,KIAA2022,KIF16B,KIF1B,KITLG,KLHL24,KRT79,LIMCH1,LRAT,LXN,MARCKSL1,MAVS,MCART1,MCHR1,METTL9,MFGE8,MICAL2,MIOX,MMD,MNAT1,MORC4,MSC,MT2A,MTL5,MYH4,MYL12B,MYOZ2,MYT1,NAPB,NCKAP1,NDNL2,NDP,NECAB3,NF1,NGFR,NIPSNAP3A,NKAPL,NOTCH4,OGFRL1,OLIG2,OXR1,PATZ1,PDE12,PEX5L,PFKFB3,PFN2,PGM1,PIAS2,PLA2G2D,PLDN,POLR1B,PPL,PPM1B,PRDX6,PRSS12,PSMD14,PTX3,QSER1,RAB20,RASA2,RDH10,RFK,RND3,RPS18,RPS6KL1,RPUSD1,RRP8,RYR3,S100A5,SEP15,SERPINA1,SERPINA10,SERPINB5,SFMBT1,SFMBT2,SLC12A2,SLC15A5,SLC16A3,SLC24A3,SLC34A1,SLC5A7,SLC6A20,SNCA,SPSB4,SRSF10,ST6GALNAC2,STRA6,SUSD2,SYAP1,TCF7,TFG,THRB,TJP2,TMEM30B,TMEM54,TNFRSF11B,TRAF1,TRH,TRIM3,TUBG2,UBD,UBE2K,USP33,USP45,VAV3,WDR78,ZBTB1,ZWINT GENE_SYMBOLS ACHE,ACTL7A,ADAM9,ALB,AMFR,ANKH,ANXA1,AP3S1,APEX1,ARHGAP24,ATP11B,ATP1B3,BARHL1,BCS1L,BEST2,BEX1,BIRC2,BLCAP,BNIPL,BST1,CCDC186,C12orf29,MISP,C3,ABHD18,CCDC88A,CCL19,CD2AP,CDH11,CDKN1A,CELSR3,CFB,CHD1L,CHST4,CLDN19,CLDN6,CLEC5A,COCH,COMMD9,CRIP3,CRTAP,CSF2RB,CSN2,CSN3,CTNNB1,CYTH3,DCLK1,DEPTOR,DERL1,DGUOK,DHX9,DIO1,DSC3,DTX1,EEPD1,EHD3,ENPP2,ESRRB,EXOSC4,EXTL1,FABP4,FADS2,RETREG2,FAM13B,FAM184B,CCSER2,FAM3D,FBP2,FCAMR,FNDC7,GBA1,GDA,GGPS1,GJA1,GLP1R,GPX6,GSR,GSTA3,GSTM1,GTF2IRD1,HAS2,HES3,MFSD14B,HOMER2,HSPA14,IGF1R,IL20,IL7R,ITIH5,KCNA3,KCND3,CEMIP,GPALPP1,NEXMIF,KIF16B,KIF1B,KITLG,KLHL24,KRT79,LIMCH1,LRAT,LXN,MARCKSL1,MAVS,SLC25A51,MCHR1,METTL9,MFGE8,MICAL2,MIOX,MMD,MNAT1,MORC4,MSC,MT2A,TESMIN,MYH4,MYL12B,MYOZ2,MYT1,NAPB,NCKAP1,NSMCE3,NDP,NECAB3,NF1,NGFR,NIPSNAP3A,NKAPL,NOTCH4,OGFRL1,OLIG2,OXR1,PATZ1,PDE12,PEX5L,PFKFB3,PFN2,PGM1,PIAS2,PLA2G2D,BLOC1S6,POLR1B,PPL,PPM1B,PRDX6,PRSS12,PSMD14,PTX3,QSER1,RAB20,RASA2,RDH10,RFK,RND3,RPS18,RPS6KL1,RPUSD1,RRP8,RYR3,S100A5,SELENOF,SERPINA1,SERPINA10,SERPINB5,SFMBT1,SFMBT2,SLC12A2,SLC15A5,SLC16A3,SLC24A3,SLC34A1,SLC5A7,SLC6A20,SNCA,SPSB4,SRSF10,ST6GALNAC2,STRA6,SUSD2,SYAP1,TCF7,TFG,THRB,TJP2,TMEM30B,TMEM54,TNFRSF11B,TRAF1,TRH,TRIM3,TUBG2,UBD,UBE2K,USP33,USP45,VAV3,DNAI4,ZBTB1,ZWINT FOUNDER_NAMES