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Expression profiling comparisons of human CD4+ T cells treated with RORgt inhibitors

ABSTRACT: The aim of this study was to identify differential gene expression resulting from the inhibition of RORgt in human CD4+ T cells. Human CD4+ T cells were cultured with anti-CD3/anti-CD28 mAb for 20 to 60 hours concurrent with exposure to Vehicle (DMSO), TMP778 (0.2 uM) or TMP776 (0.2 uM). All samples were then processed for RNA extraction, labeling, and hybridization to Affymetrix arrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Scott Davis

PROVIDER: E-GEOD-53455 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Pharmacologic inhibition of RORγt regulates Th17 signature gene expression and suppresses cutaneous inflammation in vivo.

Skepner Jill J Ramesh Radha R Trocha Mark M Schmidt Darby D Baloglu Erkan E Lobera Mercedes M Carlson Thaddeus T Hill Jonathan J Orband-Miller Lisa A LA Barnes Ashley A Boudjelal Mohamed M Sundrud Mark M Ghosh Shomir S Yang Jianfei J

Journal of immunology (Baltimore, Md. : 1950) 20140210 6

IL-17-producing CD4(+)Th17 cells, CD8(+)Tc17 cells, and γδ T cells play critical roles in the pathogenesis of autoimmune psoriasis. RORγt is required for the differentiation of Th17 cells and expression of IL-17. In this article, we describe a novel, potent, and selective RORγt inverse agonist (TMP778), and its inactive diastereomer (TMP776). This chemistry, for the first time to our knowledge, provides a unique and powerful set of tools to probe RORγt-dependent functions. TMP778, but not TMP776 ...[more]

PMID: 24516202

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