Table 3.

STING-associated diseases

Type of disease or condition	Specific disease	Mechanism of disease related to STING	Refs.
Tumor	Gliomas	STING is epigenetically silenced in gliomas in a developmentally conserved way and can be rescued by methyltransferase inhibition	294
	Tumors with defective mismatch repair (dMMR)	Loss of the MutLα subunit MLH1 generates the release of nuclear DNA into the cytoplasm, activating the cGAS–STING pathway	295,296
	Triple-negative breast cancer	STING–TBK1–IRF3 pathway activation in cancer cells governs CD8+ T cell recruitment and antitumor efficacy	297
	Merkel cell carcinoma (MCC)	STING deficiency contributes to the immune suppressive nature of MCC	104
	Pancreatic tumorigenesis	Ferroptotic damage promotes pancreatic tumorigenesis through a STING-dependent pathway	298
Viral Infection	HBV infection	The physiological lack of the functional STING pathway in hepatocytes hampers efficient innate control of HBV infection	105
	Human immunodeficiency virus (HIV)-1 infection	HIV-1 nonstructural protein can suppress antiviral immunity for immune evasion by targeting STING	199
	Influenza A virus (IAV) infection	A STING-dependent, cGAS-independent pathway is important for full interferon production and antiviral control of IAV	106
	COVID-19	cGAS–STING signalling is a critical driver of aberrant type I IFN responses in COVID-19	201
	Human rhinoviruses infection	Replication of Human rhinoviruse A serotypes is strictly dependent on STING	114,115
Bacterial infection	Mycobacterium tuberculosis infection	STING deficiency resulted in increased bacterial survival inside macrophages	299
	Brucella abortus infection	Lack of STING renders macrophages in inefficient to kill Brucella, resulting in an increased bacterial burden	300
Protozoan parasites infection	Plasmodium infection	Genomic DNA from Plasmodium falciparum, as the hemozoin-associated cargo, may access the cytosol due to phagosomal destabilization and triggers the cGAS–STING pathway	301
	Toxoplasma gondii infection	IRF3-mediated STING signaling is essential for T. gondii replication	302
	Leishmania infection	STING-mediated IFN-β production enhances the intracellular survival of Leishmania	303
	Trypanosoma cruzi infection	STING agonist as the immunological adjuvant protects against infection by different T. cruzi strains	304
Autoimmune diseases	STING-associated vasculopathy with onset in infancy (SAVI)	Disease caused by several gain-of-function mutations in STING1	12
	Aicardi–Goutières syndrome (AGS)	A subset of AGS eticological genes leads to cytosolic nucleic acid accumulatio and cGAS-STING pathway activation	162
	Familial chilblain lupus	A heterozygous gain-of-function mutation in STING can cause familial chilblain lupus	207
	COPA syndrome	Aberrant activation of the STING pathway due to its deficient retrograde from Golgi to ER	120–123
	Niemann–Pick disease type C	Knockout of NPC1 ‘primes’ STING signalling by ‘tethering’ STING to SREBP2 trafficking and blocking STING lysosomal degradation	97
	Systemic lupus erythematosus	Subset of patients has elevated cGAMP levels.	305
	Rheumatoid arthritis	Reduced cytokine expression in patient cells following cGAS or STING knockdown	306
Neurological disorders	Parkinson disease	Inflammatory phenotype in mice model is completely rescued by concurrent loss of STING	210
	Huntington’s disease	cGAS promotes the inflammatory and autophagy responses in Huntington’s disease	212
	Amyotrophic lateral sclerosis (ALS)	TDP-43 causes inflammation in ALS by stimulating mitochondrial DNA release and cGAS/STING pathway activation	211
	Multiple sclerosis	Activation of the STING attenuates experimental autoimmune encephalitis, a model of multiple sclerosis	307
	Chronic pain	Mice lacking STING or IFN-I signalling exhibit hypersensitivity to nociceptive stimuli and heightened nociceptor excitability	209
	Aautistic-like behaviors	Deficiency of STING signaling in the embryonic cerebral cortex leads to neurogenic abnormalities and autistic-like behaviors	208
Cardiovascular diseases	Myocardial infarction	Protection in cGAS-deficient mice or mice receiving STING inhibitor treatment	213–215
	Atherosclerosis	Loss of STING reduces atherosclerotic lesions, macrophage accumulation in plaques, and inflammatory molecules in mouse models	217
	Aortic aneurysm and dissection (AAD)	The presence of cytosolic DNA and subsequent activation of STING signaling represent a key mechanism in aortic degeneration	216
	Cardiac hypertrophy	Genetic or pharmacologic inhibition of the myocardial mitochondria–STING–NF-κB axis prevents chronic kidney disease (CKD)-associated cardiac hypertrophy	308
Metabolic diseases	Obesity	cGAS–cGAMP–STING pathway plays an important role in mediating obesity-induced metabolic dysfunction	164
	Type 2 diabetes	Global STING knockout beneficially alleviates insulin resistance and glucose intolerance induced by a high-fat diet, but STING knockout in islet cells impairs its glucose-stimulated insulin secretion	161
	Nonalcoholic steatohepatitis (NAFLD)	STING-mediated inflammation in Kupffer cells and monocyte-derived macrophages contributes to the progression of NAFLD	223,309
Digestive system diseases	Acute pancreatitis	STING senses DNA from dying acinar cells and promotes inflammation in a mouse model of acute pancreatitis	220
	Chronic pancreatitis	Unlike acute pancreatitis, STING activation protects chronic pancreatitis by diminishing the generation of IL-17A	221
	Inflammatory Colitis	STING knockout mice are highly susceptible to dextran sodium sulfate-induced colitis and T-cell-induced colitis	219
Aging	Senescence and aging	Protection against senescence seen in cGAS-deficient or STING-deficient cells or mice	225,310,311

cGAMP cyclic GMP–AMP, cGAS cyclic GMP–AMP synthase, IRF3 interferon regulatory factor 3, MLH1 mutL homolog 1, NPC1 NPC intracellular cholesterol transporter 1, STING stimulator of interferon genes, TDP-43 transactive response DNA binding protein 43, SREBP2 sterol regulatory element binding protein 2.