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

GABPA directly regulates STING transcription and amplifies antiviral and inflammatory responses via IKKε-mediated phosphorylation in macrophages.

• Why it matters: Understanding the transcriptional control of STING is crucial for developing targeted therapies for inflammatory diseases and interferonopathies, as posttranslational regulation is well known but transcriptional mechanisms are unclear.
• What they did: The study used molecular and cellular approaches to identify GABPA as a key transcription factor binding the Sting1 promoter, and demonstrated that IKKε phosphorylates GABPA at S447 to enhance its activity, with experiments in mice and human cells.
• The result: GABPA deficiency protects mice from colitis, and elevated GABPA correlates with STING hyperactivation in IBD and SLE patients; a GABPA-blocking peptide suppresses IFN-β in SLE PBMCs, suggesting therapeutic potential.