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10.1016/j.immuni.2014.04.004 http://scihub22266oqcxt.onion/10.1016/j.immuni.2014.04.004 C4066874!4066874 !24745332     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24745332 &cmd=llinks): Failed to open stream: HTTP request failed! 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Small-molecule ROR?t antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms |pdf=|usr=}}{{24745332 }} gab.com Text Small-molecule ROR t antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms JO: Immunity http://www.kidney.de/pget.php?&tw=1&pmid=24745332 #FOAvip We identified three retinoid-related orphan receptor gamma t (ROR?t)-specific inhibitors that suppress T helper 17 (Th17) cell responses, including Th17-cell-mediated autoimmune disease. We systemically characterized ROR?t binding in the presence and absence of drugs with corresponding whole-genome transcriptome sequencing. ROR?t acts as a direct activator of Th17 cell signature genes and a direct repressor of signature genes from other T cell lineages; its strongest transcriptional effects are on cis-regulatory sites containing the ROR? binding motif. ROR?t is central in a densely interconnected regulatory network that shapes the balance of T cell differentiation. Here, the three inhibitors modulated the ROR?t-dependent transcriptional network to varying extents and through distinct mechanisms. Whereas one inhibitor displaced ROR?t from its target loci, the other two inhibitors affected transcription predominantly without removing DNA binding. Our work illustrates the power of a system-scale analysis of transcriptional regulation to characterize potential therapeutic compounds that inhibit pathogenic Th17 cells and suppress autoimmunity. Twit Text FOAVip Small-molecule ROR t antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms ????Immunity http://www.kidney.de/pget.php?&tw=1&pmid=24745332 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24745332 #FOAvip English Wikipedia <ref>{{Cite pmid|24745332 }}</ref> Small-molecule ROR?t antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms #MMPMID24745332 Xiao S ; Yosef N ; Yang J ; Wang Y ; Zhou L ; Zhu C ; Wu C ; Baloglu E ; Schmidt D ; Ramesh R ; Lobera M ; Sundrud MS ; Tsai PY ; Xiang Z ; Wang J ; Xu Y ; Lin X ; Kretschmer K ; Rahl PB ; Young RA ; Zhong Z ; Hafler DA ; Regev A ; Ghosh S ; Marson A ; Kuchroo VK Immunity 2014[Apr]; 40 (4 ): 477-89 PMID24745332 show ga We identified three retinoid-related orphan receptor gamma t (ROR?t)-specific inhibitors that suppress T helper 17 (Th17) cell responses, including Th17-cell-mediated autoimmune disease. We systemically characterized ROR?t binding in the presence and absence of drugs with corresponding whole-genome transcriptome sequencing. ROR?t acts as a direct activator of Th17 cell signature genes and a direct repressor of signature genes from other T cell lineages; its strongest transcriptional effects are on cis-regulatory sites containing the ROR? binding motif. ROR?t is central in a densely interconnected regulatory network that shapes the balance of T cell differentiation. Here, the three inhibitors modulated the ROR?t-dependent transcriptional network to varying extents and through distinct mechanisms. Whereas one inhibitor displaced ROR?t from its target loci, the other two inhibitors affected transcription predominantly without removing DNA binding. Our work illustrates the power of a system-scale analysis of transcriptional regulation to characterize potential therapeutic compounds that inhibit pathogenic Th17 cells and suppress autoimmunity. |Androstenols/chemistry [MESH] |Animals [MESH] |Benzeneacetamides/chemistry/*pharmacology [MESH] |Benzhydryl Compounds/chemistry/*pharmacology [MESH] |Cell Differentiation/drug effects [MESH] |Cell Line, Tumor [MESH] |Cell Lineage/drug effects [MESH] |Cytokines/metabolism [MESH] |Digoxin/chemistry/*pharmacology [MESH] |Encephalomyelitis, Autoimmune, Experimental/*drug therapy/immunology [MESH] |Gene Regulatory Networks/*drug effects [MESH] |Heterocyclic Compounds, 4 or More Rings/chemistry/*pharmacology [MESH] |Humans [MESH] |Mice [MESH] |Mice, Inbred C57BL [MESH] |Mice, Knockout [MESH] |Multiple Sclerosis/*drug therapy/immunology [MESH] |Myelin-Oligodendrocyte Glycoprotein/immunology [MESH] |Nuclear Receptor Subfamily 1, Group F, Member 3/*antagonists & inhibitors/genetics [MESH] |Peptide Fragments/immunology [MESH] |Protein Binding/drug effects [MESH] |Structure-Activity Relationship [MESH] |Systems Biology [MESH] |T-Lymphocyte Subsets/*drug effects/immunology [MESH] |Th17 Cells/*drug effects/immunology [MESH] |Transcription, Genetic/drug effects [MESH]Small-molecule ROR?t antagonists inhibit T helper 17 cell transcriptio(epmc).pdf DeepDyve Pubget Overpricing