STANDARD_NAME GSE2706_UNSTIM_VS_2H_LPS_DC_DN SYSTEMATIC_NAME M4696 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE2706_UNSTIM_VS_2H_LPS_DC_DN NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes down-regulated in comparison of unstimulated dendritic cells (DC) at 0 h versus DCs stimulated with LPS (TLR4 agonist) for 2 h. DESCRIPTION_FULL Toll like receptors (TLRs) sense microbial products and initiate adaptive immune responses by activating dendritic cells (DCs). Since pathogens may contain several agonists we asked whether different TLRs may synergize in DC activation. We report that in human and mouse DC TLR3 or TLR4 potently synergize with TLR7, TLR8 or TLR9 in the induction of selected cytokine genes. Upon synergistic stimulation, IL-12, IL-23 and Delta-4 are induced at levels 50-100 fold higher than those induced by optimal concentrations of single agonists, leading to enhanced and sustained TH1 polarizing capacity. Using microarray analysis we show that only 1.5% of the transcripts induced by single TLR agonists are synergistically regulated by combinations of TLR4 and TLR8 agonists. These results identify a combinatorial code by which DCs discriminate pathogens and provide (suggest) a rationale to design adjuvants for TH1 responses. Series_overall_design: 3 untreated, 3 treated with LPS at 2h, 3 treated with LPS at 8h, 3 treated with R848 at 2h, 3 treated with R848 at 8h, 3 treated with LPS + R848 at 2h, 3 treated with LPS + R848 at 8h PMID 15995707 GEOID GSE2706 AUTHORS Napolitani G,Rinaldi A,Bertoni F,Sallusto F,Lanzavecchia A CONTRIBUTOR Jernej Godec CONTRIBUTOR_ORG Dana-Farber Cancer Institute EXACT_SOURCE GSE2706_1839_200_DN FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ABCC11,ACSL1,ADA,ANKRD33B,APOBEC3A,ARL5B,ATF3,ATF5,B4GALT5,B7H6,BATF,BCL2L1,BID,BIRC3,BTG1,BTG2,BTG3,C10orf10,C11orf88,C15orf48,C17orf58,C17orf78,C1orf61,C21orf71,C6orf145,C7orf40,C9orf30,CCRL2,CD274,CD80,CDKN1A,CFLAR,CITED1,CRLF2,CSRNP1,CXCL1,CXCL10,CXCL11,CXCL2,CXCL3,DCUN1D3,DEFB124,DKFZp686L14188,DNAAF1,DUSP2,DUSP5,EDN1,EFNA1,EHD1,ELL2,EPM2AIP1,ERICH1,ETV3,EZH2,FAM43A,FXYD6,GADD45A,GADD45B,GALNT3,GATA6,GBP1,GEM,GMEB1,GPR132,GPR183,GPR45,HCAR3,HERC6,HES4,HIVEP1,HS3ST3B1,ICAM1,IFI44,IFIH1,IFIT1,IFIT3,IFNB1,IL10,IL10RA,IL12B,IL18RAP,IL1A,IL23A,IL36G,IL6,INADL,INHBA,INSIG1,IRAK2,IRF1,IRF7,IRF8,ISG15,ISG20,ITGB8,JAG1,KCNH2,KCNJ2,KDM6B,KRTAP4-9,LAMB2P1,LAMP3,LDLR,LOC100128185,LOC100130232,LOC283567,LOC285628,LOC374443,LOC401317,LOC440896,LOC731424,LRRC32,LTA,MAP2K3,MAP3K8,MARCKSL1,MFSD2A,MGC12916,MGC4859,MIR155HG,NAMPT,NCF1C,NCRNA00152,NFKB1,NFKBIA,NFKBIB,NFKBIZ,NINJ1,NR4A3,NUP98,OASL,OBFC2A,OTUD1,P2RX7,P2RY2,PAPD7,PAPPA2,PARP14,PELI1,PIK3R5,PIM3,PLAGL2,PLAUR,PML,PTGER4,PTGIR,PTP4A3,PTPN1,PTPN5,RAB21,RAB30,RAB7B,RAPGEF2,RASGRP1,RASSF5,REL,RELB,RGS1,RILPL2,RIPK2,RMST,RNF144B,SAR1A,SELK,SHROOM4,SIAH2,SLC2A6,SLC43A3,SOCS3,SOD2,SPAG1,SPRED2,STX11,TAP1,TDH,TMEM150C,TMEM194A,TNFAIP2,TNFAIP3,TNFAIP6,TNFAIP8,TNFRSF4,TNIP1,TNIP2,TNIP3,TP53BP2,TP53INP2,TRAF1,TRIM26,TTN,TTYH2,TUBB2A,UBE2Z,USP12,WNT2,ZC3H12A,ZC3HAV1,ZNF385B,ZNF697,ZNFX1 GENE_SYMBOLS ABCC11,ACSL1,ADA,ANKRD33B,APOBEC3A,ARL5B,ATF3,ATF5,B4GALT5,,BATF,BCL2L1,BID,BIRC3,BTG1,BTG2,BTG3,DEPP1,HOATZ,C15orf48,C17orf58,C17orf78,MIR9-1HG,,PXDC1,SNHG15,MSANTD3,CCRL2,CD274,CD80,CDKN1A,CFLAR,CITED1,CRLF2,CSRNP1,CXCL1,CXCL10,CXCL11,CXCL2,CXCL3,DCUN1D3,DEFB124,,DNAAF1,DUSP2,DUSP5,EDN1,EFNA1,EHD1,ELL2,EPM2AIP1,ERICH1,ETV3,EZH2,FAM43A,FXYD6,GADD45A,GADD45B,GALNT3,GATA6,GBP1,GEM,GMEB1,GPR132,GPR183,GPR45,HCAR3,HERC6,HES4,HIVEP1,HS3ST3B1,ICAM1,IFI44,IFIH1,IFIT1,IFIT3,IFNB1,IL10,IL10RA,IL12B,IL18RAP,IL1A,IL23A,IL36G,IL6,PATJ,INHBA,INSIG1,IRAK2,IRF1,IRF7,IRF8,ISG15,ISG20,ITGB8,JAG1,KCNH2,KCNJ2,KDM6B,KRTAP4-9,LAMB2P1,LAMP3,LDLR,,,SIPA1L1,MIR3142HG,ENSG00000291107,CREB5,LINC03025,MIR3945HG,LRRC32,LTA,MAP2K3,MAP3K8,MARCKSL1,MFSD2A,,MGC4859,MIR155HG,NAMPT,NCF1C,CYTOR,NFKB1,NFKBIA,NFKBIB,NFKBIZ,NINJ1,NR4A3,NUP98,OASL,NABP1,OTUD1,P2RX7,P2RY2,TENT4A,PAPPA2,PARP14,PELI1,PIK3R5,PIM3,PLAGL2,PLAUR,PML,PTGER4,PTGIR,PTP4A3,PTPN1,PTPN5,RAB21,RAB30,RAB7B,RAPGEF2,RASGRP1,RASSF5,REL,RELB,RGS1,RILPL2,RIPK2,RMST,RNF144B,SAR1A,SELENOK,SHROOM4,SIAH2,SLC2A6,SLC43A3,SOCS3,SOD2,SPAG1,SPRED2,STX11,TAP1,TDH,TMEM150C,NEMP1,TNFAIP2,TNFAIP3,TNFAIP6,TNFAIP8,TNFRSF4,TNIP1,TNIP2,TNIP3,TP53BP2,TP53INP2,TRAF1,TRIM26,TTN,TTYH2,TUBB2A,UBE2Z,USP12,WNT2,ZC3H12A,ZC3HAV1,ZNF385B,ZNF697,ZNFX1 FOUNDER_NAMES