Chemical Inhibition of the RORγt-dependent Transcriptional Network in Th17 cells [ChIP-Seq]

ABSTRACT: RORγt is a transcription factor required for T helper 17 (Th17) cell development. We identified three RORγt-specific inhibitors that suppress Th17 cell responses including Th17 cell-mediated autoimmune disease. We systemically characterized RORγt binding data in the presence and absence of drug with corresponding whole-transcriptome sequencing for wild-type and RORγt-deficient cells. RORγt is central in a densely interconnected regulatory network, acting both as a direct activator of genes important for Th17 cell differentiation and as a direct repressor of genes from other T-cell lineages. The three inhibitors identified here reversed both of these modes of action, but to varying extents and through distinct mechanisms. Whereas one inhibitor displaced RORγt from its target-loci, the two m

ORGANISM(S): Mus musculus

SUBMITTER: Nir Yosef 

PROVIDER: E-GEOD-56019 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress