Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome

Individuals with Down syndrome have a increased likelihood of suffering from inflammatory and autoimmune conditions, due to the presence of four interferon receptors on chromosome 21. Transcription of genes plays a key role in the interferon response, and the Mediator kinases, CDK8 and CDK19, are essential in potentiating this transcription. Given the role CDK8/19 play in the interferon response, and the fact that selective inhibitors of these kinases exist (such as Cortistatin A), it is possible that targetting Mediator kinase activity may alleviate symptoms of chronic inflammation in Down syndrome. Overall design: Examination of effects of Mediator kinase inhibition (through treatment with selective inhibitor Cortistatin A) and interferon gamma stimulation on transcription (through RNA-seq) in cell lines from a pair of siblings, one with Down syndrome and one without