STING1, also known as STING or TMEM173, is an endoplasmic reticulum (ER) protein. It plays a fundamental role in the production of type I interferons (IFNs) and pro-inflammatory cytokines by activating multiple transcription factors in response to microbial or host-derived DNA. It is a key component of the cGAS-STING pathway, which is crucial for innate immunity, and its dysregulation is associated with various diseases [1]. Genetic models, such as KO mouse models, are valuable for studying its functions.

In a study on nephrotoxic nephritis, Sting1-/- mice had lower kidney cytokine expression, milder kidney infiltration by immune cells, and decreased disease severity compared to wild-type mice. This indicates that STING1 activation is a pathological mechanism in rapidly progressive/crescentic glomerulonephritis (RPGN/CGN) [1].

In conclusion, STING1 is essential for the production of IFNs and pro-inflammatory cytokines via the cGAS-STING pathway, playing a crucial role in innate immunity. The use of Sting1 KO mouse models has revealed its significance in diseases like RPGN/CGN, providing insights into potential therapeutic targets for such immune-mediated diseases.

References:

1. García-Giménez, Jorge, Córdoba-David, Gina, Rayego-Mateos, Sandra, Ortiz, Alberto, Ramos, Adrián M. 2023. STING1 deficiency ameliorates immune-mediated crescentic glomerulonephritis in mice. In The Journal of pathology, 261, 309-322. doi:10.1002/path.6177. https://pubmed.ncbi.nlm.nih.gov/37650295/