STANDARD_NAME	GSE8685_IL2_STARVED_VS_IL2_ACT_IL2_STARVED_CD4_TCELL_DN
SYSTEMATIC_NAME	M325
COLLECTION	C7:IMMUNESIGDB
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE8685_IL2_STARVED_VS_IL2_ACT_IL2_STARVED_CD4_TCELL_DN
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes down-regulated in Sez-2 cells (T cell lymphoma): untreated versus IL2 [GeneID=3558].
DESCRIPTION_FULL	In this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells.
PMID	18281483
GEOID	GSE8685
AUTHORS	Marzec M,Halasa K,Kasprzycka M,Wysocka M,Liu X,Tobias JW,Baldwin D,Zhang Q,Odum N,Rook AH,Wasik MA
CONTRIBUTOR	Jernej Godec
CONTRIBUTOR_ORG	Dana-Farber Cancer Institute
EXACT_SOURCE	GSE8685_3173_200_DN
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	ABCC4,ADAM9,AGL,ALDH2,API5,ASF1B,BID,BRI3BP,BSN,C11orf74,C12orf42,C15orf43,C16orf58,C17orf53,C1GALT1C1,C4orf19,C6orf170,C6orf48,C6orf62,C9orf82,CACNA1D,CCDC137,CCDC18,CCDC34,CCNA2,CDC14A,CDCA2,CDH1,CDK2AP1,CENPM,CES5A,CKAP2,CKAP2L,CLTA,CNNM2,CPNE2,CREG2,CRELD2,CSF3R,CSTF3,CTC1,DAGLB,DBI,DCLRE1B,DEPDC1,DEPTOR,DHX9,DKC1,DNMT1,DOCK1,DOLK,DTWD1,EEPD1,EIF4H,ELANE,EME1,ENOPH1,ERLIN1,ERLIN2,ESCO2,FADS2,FAM111A,FAM184A,FAM98B,FANCB,FNIP1,FRRS1,FUCA2,FUT8,G6PD,GAB2,GABRP,GANC,GCLM,GFI1,GLIPR1,GMDS,GMPR,GORASP2,GOT2,H2AFY,HDLBP,HMGA2,HNRNPU,HPSE,HSD17B1,ICA1,IDH3A,IKBKAP,IL11RA,IL15,IL1R1,IMPA1,IMPDH2,IREB2,KBTBD13,KIAA1549,KIFAP3,KPNA2,KPNB1,KRR1,KRTAP2-4,LEO1,LOC155060,LRRC58,LUC7L3,MANEA,MAPK7,MAPK8,MDM1,MED6,MEIS1,MIER3,MIS18BP1,MMP2,MORF4L1,MOSPD2,MTM1,NAT8L,NEDD4,NEK2,NEO1,NPM1,NUP43,OAF,OAZ1,PARL,PCM1,PDE6D,PHLDB2,PKIB,POLA2,POLR1A,POLR1D,PRIM2,PSME4,PXT1,QTRTD1,RAB11FIP5,RACGAP1,RAD54B,RAI14,RBM44,RELL1,RFWD3,RNASEH2B,RNF144B,RNF157,RNF7,RPGR,RRM1,SCML2,SCOC,SDF2L1,SEC23B,SEC24D,SEPHS1,SEPHS2,SERBP1,SERPINF1,SH3D19,SKA3,SLC22A3,SLC31A1,SNHG3,SNORD47,SNX9,SOX12,SPAG5,SPNS2,SRD5A1,SRRM1,SSX2IP,STX3,TBC1D24,TBC1D2B,THG1L,TIMELESS,TKT,TM6SF1,TMEM144,TMEM38B,TMEM8B,TOMM6,TRIM35,TWISTNB,TYMS,UBE2Q2,UGDH,UMOD,UNC5B,USP11,VAPA,WHSC1,ZBED5,ZDHHC5,ZFP41,ZNF330,ZNF446,ZWILCH
GENE_SYMBOLS	ABCC4,ADAM9,AGL,ALDH2,API5,ASF1B,BID,BRI3BP,BSN,IFTAP,C12orf42,TERB2,RUSF1,HROB,C1GALT1C1,PGCKA1,TBC1D32,SNHG32,C6orf62,CAAP1,CACNA1D,CCDC137,CCDC18,CCDC34,CCNA2,CDC14A,CDCA2,CDH1,CDK2AP1,CENPM,CES5A,CKAP2,CKAP2L,CLTA,CNNM2,CPNE2,CREG2,CRELD2,CSF3R,CSTF3,CTC1,DAGLB,DBI,DCLRE1B,DEPDC1,DEPTOR,DHX9,DKC1,DNMT1,DOCK1,DOLK,DTWD1,EEPD1,EIF4H,ELANE,EME1,ENOPH1,ERLIN1,ERLIN2,ESCO2,FADS2,FAM111A,FAM184A,FAM98B,FANCB,FNIP1,FRRS1,FUCA2,FUT8,G6PD,GAB2,GABRP,GANC,GCLM,GFI1,GLIPR1,GMDS,GMPR,GORASP2,GOT2,MACROH2A1,HDLBP,HMGA2,HNRNPU,HPSE,HSD17B1,ICA1,IDH3A,ELP1,IL11RA,IL15,IL1R1,IMPA1,IMPDH2,IREB2,KBTBD13,KIAA1549,KIFAP3,KPNA2,KPNB1,KRR1,KRTAP2-4,LEO1,,LRRC58,LUC7L3,MANEA,MAPK7,MAPK8,MDM1,MED6,MEIS1,MIER3,MIS18BP1,MMP2,MORF4L1,MOSPD2,MTM1,NAT8L,NEDD4,NEK2,NEO1,NPM1,NUP43,OAF,OAZ1,PARL,PCM1,PDE6D,PHLDB2,PKIB,POLA2,POLR1A,POLR1D,PRIM2,PSME4,PXT1,QTRT2,RAB11FIP5,RACGAP1,RAD54B,RAI14,RBM44,RELL1,RFWD3,RNASEH2B,RNF144B,RNF157,RNF7,RPGR,RRM1,SCML2,SCOC,SDF2L1,SEC23B,SEC24D,SEPHS1,SEPHS2,SERBP1,SERPINF1,SH3D19,SKA3,SLC22A3,SLC31A1,SNHG3,,SNX9,SOX12,SPAG5,SPNS2,SRD5A1,SRRM1,SSX2IP,STX3,TBC1D24,TBC1D2B,THG1L,TIMELESS,TKT,TM6SF1,TMEM144,TMEM38B,TMEM8B,TOMM6,TRIM35,POLR1F,TYMS,UBE2Q2,UGDH,UMOD,UNC5B,USP11,VAPA,NSD2,ZBED5,ZDHHC5,ZFP41,ZNF330,ZNF446,ZWILCH
FOUNDER_NAMES