Small-Molecule RORγt Antagonists Inhibit T Helper 17 Cell Transcriptional Network by Divergent Mechanisms
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. Small-Molecule RORγt Antagonists Inhibit T Helper 17 Cell Transcriptional Network by Divergent Mechanisms. Immunity 2014, 40: 477-489. PMID: 24745332, PMCID: PMC4066874, DOI: 10.1016/j.immuni.2014.04.004.Peer-Reviewed Original ResearchMeSH KeywordsAndrostenolsAnimalsBenzeneacetamidesBenzhydryl CompoundsCell DifferentiationCell Line, TumorCell LineageCytokinesDigoxinEncephalomyelitis, Autoimmune, ExperimentalGene Regulatory NetworksHeterocyclic Compounds, 4 or More RingsHumansMiceMice, Inbred C57BLMice, KnockoutMultiple SclerosisMyelin-Oligodendrocyte GlycoproteinNuclear Receptor Subfamily 1, Group F, Member 3Peptide FragmentsProtein BindingStructure-Activity RelationshipSystems BiologyT-Lymphocyte SubsetsTh17 CellsTranscription, GeneticTranscriptional ActivationConceptsTranscriptional networksSignature genesCis-regulatory sitesStrong transcriptional effectsInterconnected regulatory networkCell signature genesSystem-scale analysisTranscriptional regulationDirect repressorTarget lociTranscriptome sequencingRegulatory networksDNA bindingTranscriptional effectsCell lineagesCell differentiationT-cell lineageDirect activatorDivergent mechanismsT cell differentiationSpecific inhibitorDistinct mechanismsPotential therapeutic compoundsGenesRetinoid-related orphan receptor gamma t