Researchers in a recent study investigated the role of the stimulator of interferon genes (STING) in the development of systemic lupus erythematosus (SLE) and associated atherosclerosis, using murine models driven by Toll-like receptor 7 (TLR7) activation. Researchers induced a lupus-like condition in wild-type and STING knockout (Sting1-/-) mice using imiquimod and evaluated immune responses, organ involvement, and vascular pathology. STING deficiency significantly reduced disease severity, including splenomegaly, kidney damage, immune cell activation, and IFN-β production. Additional experiments using Apoe-/- mice on a high-fat diet demonstrated that STING knockout mice had less vascular damage and a lower burden of atherosclerosis.
The findings suggest that STING plays a critical role in amplifying TLR7-driven autoimmunity and vascular damage through enhanced type I interferon signaling. STING-deficient mice showed muted inflammatory responses even when exposed to DNA stimuli, implicating STING in the regulation of both lupus pathogenesis and atherogenesis. Human data further supported these results, with increased IFN-I activity linked to lipid uptake in macrophages and oxidized nucleic acid levels correlating with disease activity in patients with SLE. Together, these results support the therapeutic potential of targeting STING to mitigate both autoimmune and cardiovascular complications in SLE.
Reference: Liu Y, Carmona-Rivera C, Seto NL, et al. Role of STING Deficiency in Amelioration of Mouse Models of Lupus and Atherosclerosis. Arthritis Rheumatol. 2025 May;77(5):547-559. doi: 10.1002/art.43062. Epub 2024 Dec 19. PMID: 39605244; PMCID: PMC12039466.
