Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome III

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) on transcription (through RNA-seq) in two T21 lymphoblastoid cell lines, one collected at 24 hours from a sibling to a D21 cell line previously analyzed by the lab, and one collected at 4.5 hours in a non-sibling T21 cell line.