Activation of ACE2 and interferon-stimulated transcriptomes in human airway epithelium is curbed by Janus Kinase inhibitors.

SARS-CoV-2 infection of human airway epithelium activates genetic programs that lead to progressive hyperinflammation in COVID-19 patients. Here we report on the transcriptomic response of airway epithelium to interferons and its suppression by the JAK inhibitors Baricitinib and Ruxolitinib. There is a debate on the regulation of the conventional versus the novel intronic promoter inducing the short ACE2 isoform. Through RNA-seq and ChIP-seq analyses for activating chromatin marks and Polymerase II, we define the interferon-activated intronic regulatory region. Our results also support that the conventional ACE2 promoter is controlled by interferon.