Pro-inflammation Associated with a Gain-of-Function Mutation (R284S) in the Innate Immune Sensor STING

Hiroyasu Konno, Ivan K. Chinn, Diana Hong, Jordan S. Orange, James R. Lupski, Alejandra Mendoza, Luis A. Pedroza, Glen N Barber

Research output: Contribution to journalArticle

20 Scopus citations


The cellular sensor stimulator of interferon genes (STING) initiates type I interferon (IFN) and cytokine production following association with cyclic dinucleotides (CDNs) generated from intracellular bacteria or via a cellular synthase, cGAS, after binding microbial or self-DNA. Although essential for protecting the host against infection, unscheduled STING signaling is now known to be responsible for a variety of autoinflammatory disorders. Here, we report a gain-of-function mutation in STING (R284S), isolated from a patient who did not require CDNs to augment activity and who manifested a constitutively active phenotype. Control of the Unc-51-like autophagy activating kinase 1 (ULK1) pathway, which has previously been shown to influence STING function, was potently able to suppress STING (R284S) activity to alleviate cytokine production. Our findings add to the growing list of inflammatory syndromes associated with spontaneous STING signaling and provide a therapeutic strategy for the treatment of STING-induced inflammatory disease. Konno et al. characterize a gain-of-function mutation in the innate immune sensor STING isolated from a patient. AMPK/ULK1 regulators are able to repress constitutive STING signaling, suggesting a possible therapeutic approach for the treatment of STING-related inflammatory disease.

Original languageEnglish (US)
JournalCell Reports
StateAccepted/In press - Jan 1 2018



  • AMPK inhibitor
  • autoimmune disease
  • gain-of-function mutation
  • inflammatory disease
  • STING inhibitor
  • type I interferonopathy
  • ULK1 phosphorylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Konno, H., Chinn, I. K., Hong, D., Orange, J. S., Lupski, J. R., Mendoza, A., Pedroza, L. A., & Barber, G. N. (Accepted/In press). Pro-inflammation Associated with a Gain-of-Function Mutation (R284S) in the Innate Immune Sensor STING. Cell Reports.