The IKKε-GABPA axis regulates STING transcription to orchestrate antiviral immunity and inflammation.

GABPA transcription factor, activated by IKKε phosphorylation, enhances STING expression and amplifies antiviral and inflammatory responses in macrophages.

• Why it matters: Understanding the transcriptional regulation of STING is crucial for developing targeted therapies for inflammatory diseases and interferonopathies, where STING hyperactivation contributes to pathology.
• What they did: The study identified GABPA as a key regulator that binds directly to the Sting1 promoter, with IKKε-mediated phosphorylation at S447 boosting its activity, involving 10 key experiments including genetic and biochemical analyses.
• The result: GABPA deficiency protects mice from colitis, and its elevated expression correlates with disease severity in IBD and SLE, while a GABPA-blocking peptide shows promise as a therapeutic agent to suppress excessive interferon production.