STING1-gene

The STING1 gene, also known as the TMEM173 gene (STING1 is the acronym for "Stimulator of interferon genes 1"), is located on chromosome 5q31.2 and codes for the transmembrane adaptor protein STING. STING functions as an important regulator of the innate immune response to viral and bacterial infections. The encoded protein is a pattern recognition receptor that recognizes cytosolic nucleic acids and transmits signals that activate type I interferon responses.

STING is localized in the endoplasmic reticulum (ER), where it forms a homodimer in response to the presence of cytosolic dsDNA (Liu et al. 2014). STING1 has 5 putative N-terminal transmembrane domains, a signal cleavage site in the first transmembrane domain, and a leucine-rich region overlapping the first 4 transmembrane domains. STING is expressed in almost all tissues.

STING1 is crucial for the induction of IFN. It was found that murine embryonic fibroblasts as well as antigen-presenting cells such as macrophages and dendritic cells (exposed to intracellular B-form DNA, the DNA virus herpes simplex virus 1 (HSV-1) or the bacterium Listeria monocytogenes) require STING to initiate effective IFN production. Accordingly, Sting knockout mice were susceptible to lethal infection after exposure to HSV-1 (Chen H et al. 2011).

The importance of STING in the induction of DNA-mediated innate immune responses is also highlighted by the fact that cytotoxic T cell responses induced by plasmid DNA vaccination were reduced in Sting-deficient animals.

Overexpression of STING leads to high type I IFN induction and expression of IFN-regulated genes.

Suppression of STING reduced IFN induction and increased susceptibility to viral infections. It can be assumed that STING is an essential innate immune mediator.

Mutations in this gene lead to the clinical picture of "STING-associated vasculopathy, infantile-onset" (SAVI, OMIM:615934). Numerous mutations in the STING gene have now been identified (Liu et al. 2014).

1. Ablasser A et al. (2013) Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. Nature 503: 530-534
2. Chen H et al (2011) Activation of STAT6 by STING is critical for antiviral innate immunity. Cell 147: 436-446
3. Ishikawa H et al (2008) STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455: 674-678.
4. Liu Y et al (2014) Activated STING in a vascular and pulmonary syndrome. New Eng J Med 371: 507-518.