Table 1.

Diseases associated with cGAS/STING pathway

Disease	Relevance with the cGAS/STING signaling	References
Autoimmune and autoinflammatory diseases
Aicardi–Goutières syndrome (AGS)	Inhibition of AGS development in cGAS or STING knockout mice	Gray et al. (2015)
COPA syndrome	Reduction of type I IFN-mediated inflammation by STING deletion or pharmacological inhibition in a mouse model of COPA syndrome (CopaE241K/ +)	Deng et al. (2020)
Familial chilblain lupus	Ligand-independent homodimerization of STING and constitutive expression of type I IFN by heterozygous gain-of-function mutations in STING from familial lupus A patients	König et al. (2017)
STING-associated vasculopathy with onset in infancy (SAVI)	Three mutations in exon 5 of TMEM173 (V147L, N154S and V155M) from SAVI patients Induction of cytokine production, skin ulcerations, lung disease, and premature death by SAVI-mediated STING activation in of STING mutant knock-in mice	Liu et al. (2014), Warner et al. (2017), Bouis et al. (2019), Motwani et al. (2019), Siedel et al. (2020)
Rheumatoid arthritis (RA)	Promotion of inflammatory cytokine production in a cGAS-dependent manner in fibroblast-like synoviocytes from RA patients Reduction of migration and invasion in primary fibroblast-like synovial cells from RA patients by knockdown of cGAS or STING using siRNA in vitro Reduction of inflammatory cell infiltration and joint swelling by cGAS-deficient in an inflammatory arthritis mouse model	Wang et al. (2015b, 2019a), Li et al. (2022a), Willemsen et al. (2021)
Systemic lupus erythematosus (SLE)	In SLE patients, increase of cGAS levels in peripheral blood mononuclear cells (PBMCs) and induction of IFN-I and ISG by activation of cGAS/STING pathway in serum Exacerbation of autoimmunity by lack of cGAS and STING in 2,6,10,14-Tetramethylpentadecane (TMPD) induced chronic SLE mice	An et al. (2017), Kato et al. (2018b), Motwani et al. (2021)
Cancer
Colorectal cancer	Inhibition of inflammation in tumor by recruitment of myeloid cells through STING/type I IFN pathway in mice	Liang et al. (2017)
Gastric cancer	Reduction of STING expression in tumor tissue of gastric cancer patients Positive correlation between STING expression and survival rates of gastric cancer patient	Song et al. (2017)
Hepatocellular Carcinoma (HCC)	Increase of tumor size in STING-deficient HCC mice Impairment of immune surveillance of oncogenic RAS by deletion of STING in mice	Thomsen et al. (2020), Dou et al. (2017)
Lung cancer	Reduction of STING expression in tissues of NSCLC patients with enriched KRAS mutational status	Kitajima et al. (2019)
Prostate cancer	Stimulation of STING-dependent type I IFN expression through accumulation of cytoplasmic DNA by MUS81 in prostate cancer cells	Ho et al. (2016)
Skin cancer	Identification of low STING expression in six melanoma cell lines (MeWo, G361, WM115, SK-MEL-2, SK-MEL-5, and SK-MEL-28) Reduction of B16F10 growth and number of lung metastases by intratumoral injection of 2′,3′-cGAMP in mice Decrease of tumor size and increase of T-cell infiltration by injection of STINGVAX in B16 transplanted melanoma	Xia et al. (2016b), Demaria et al. (2015) Fu et al. (2015)
Metastasis	Promotion of brain metastasis of breast and lung cancer cells by STING activation via the STAT1 and NF-κB pathways in astrocytes Inhibition of lung metastasis by cGAMP via the EMT process and the PI3K/AKT pathway in skin tumor-bearing mice	Bakhoum et al. (2018), Lu et al. (2023)
Cardiovascular diseases
Atherosclerosis	Promotion of initiation and development of atherosclerosis by activated cGAS in ApoE knockout mice	Lu et al. (2021)
Cardiac hypertrophy	Increase of STING expression in cardiomyopathy patients (DCM, HCM) and mice cardiac hypertrophy induced by aortic banding surgery Reduction of cardiac cross-sectional area and inflammatory response by deletion of STING in mouse model of cardiac hypertrophy Reduction of inflammatory response and cardiac hypertrophy by overexpression of STING in mouse model of cardiac hypertrophy	Zhang et al. (2020), Xiong et al. (2021)
Traumatic brain injury (TBI)	Increase of STING mRNA levels in both post-mortem human TBI and mice brain undergoing controlled cortical impact surgery	Abdullah et al. (2018)
Ischemic stroke	In the mouse model of middle cerebral artery occlusion (MCAO), activation of cGAS/STING pathway by accumulation of cytoplasmic dsDNA in microglia and astrocytes Activation of cGAS/STING pathway by the release of mtDNA in the cytoplasm of microglia during ischemic stroke in mice Reduction of brain injury such as brain infarction and brain edema by inhibition of STING in mice Alleviation of ischemic stroke through suppression of microglial M1 polarization by intraperitoneal injection of STING inhibitor in MCAO mice	Li et al. (2020b), Kong et al. (2022)
Myocardial infarction (MI)	Promotion of cardiac repair through increased collagen deposition, fibrogenesis and angiogenesis by silence of cGAS in mice	Cao et al. (2018)
Kidney diseases
Acute kidney injury (AKI)	Induction of cGAS/STING pathway-meditated inflammatory response by cisplatin-induced releasement of mtDNA into the cytoplasm in HK-2 cells Attenuation of AKI in STING knockout mice	Maekawa et al. (2019)
Diabetic kidney disease (DKD)	Increase of STING levels in kidney tissues from DKD mice Increase of cGAS, STING and phosphorylated TBK1 levels in podocytes of db/db mice Induction of podocyte injury by mtDNA-mediated cGAS/STING activation in DKD or diet-induced obesity mice Alleviation of podocyte injury through genetic ablation of STING or pharmacological inhibition by C176 in db/db mice	Khedr et al. (2020), Zang et al. (2022), Mitrofanova et al. (2022a)
Chronic kidney disease (CKD)	Attenuation of renal fibrosis by deletion of STING in mice Increased plaque vulnerability by cGAS-induced type I IFN production due to mitochondrial DNA leakage in mice	Chung et al. (2019), Bi et al. (2021)
Lung diseases
Asthma	Alleviation of ovalbumin- or house dust mite-induced allergic airway inflammation in airway epithelial cell specific cGAS knockout mice	Han et al. (2020)
Chronic obstructive pulmonary disease (COPD)	In bronchoalveolar lavage fluid of mice, Releasement of mitochondrial DNA into the cytoplasm by exposure of cigarette smoke extracts	Pouwels et al. (2016)
Idiopathic pulmonary fibrosis (IPF)	Increase of cGAS and STING expression in lung epithelial cells from IPF patients Reduction of senescence markers by pharmacological cGAS inhibition by RU.521 in airway epithelial cells of IPF Increase of cGAS, STING and self-dsDNA levels in lung tissues of bleomycin-induced fibrosis mouse model Aggravation of lung fibrosis through higher collagen deposition and excessive expression of remodeling factors by deletion of STING in mice Induction of CD8+ T cells and chronic activation of type I interferon signaling and immunoproteasome in alveolar epithelial cells of IPF patients via the cGAS/STING pathway	Schuliga et al. (2021), Savigny et al. (2020), Wang et al. (2023a)
Silicosis	Increase of cGAS and STING expression by releasement of self-dsDNA by exposure of silica microparticles in mouse lungs Induction of apoptosis through silica induced STING activation in bone marrow-derived dendritic cells from mice	(Benmerzoug et al. (2018)
Metabolic disorders and non-alcoholic fatty liver disease
High-fat diet (HFD)	Activation of cGAS/STING signaling in adipocytes and iWAT of obese mice fed a HFD	(Bai et al. (2017)
Non-alcoholic fattey liver disease (NAFLD)	Enhance of STING expression in liver tissues from NAFLD patients Induction of glucose and lipid metabolism disorders by promoting liver inflammation and hepatocyte death through the cGAS/STING pathway in HFD mouse model	(Luo et al. (2018) (Qiao et al. (2018)