The cGAS–STING pathway as a therapeutic target in inflammatory diseases

Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway

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Mechanisms underlying inflammation in neurodegeneration

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STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling

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Naturally occurring p16Ink4a-positive cells shorten healthy lifespan

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STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity

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The role of senescent cells in ageing

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Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA

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A diverse range of gene products are effectors of the type I interferon antiviral response

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Senolytics improve physical function and increase lifespan in old age

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STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors

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Mitochondrial DNA stress primes the antiviral innate immune response

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Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation

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cGAS surveillance of micronuclei links genome instability to innate immunity

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CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING.

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Chromosomal instability drives metastasis through a cytosolic DNA response

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Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease

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Mitotic progression following DNA damage enables pattern recognition within micronuclei

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Activated STING in a Vascular and Pulmonary Syndrome

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Cytoplasmic chromatin triggers inflammation in senescence and cancer

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Senescent cells: an emerging target for diseases of ageing

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Trex1 prevents cell-intrinsic initiation of autoimmunity

Stetson, D. B., Ko, J. S., Heidmann, T., & Medzhitov, R. (2008) · Cell · doi:10.1016/j.cell.2008.06.032 · Cited by 1,280 · see citing works

Autophagy induction via STING trafficking is a primordial function of the cGAS pathway

Gui, X., Yang, H., Li, T., Tan, X., Shi, P., Li, M., Du, F., & Chen, Z. J. (2019) · Nature · doi:10.1038/s41586-019-1006-9 · Cited by 1,269 · see citing works

L1 drives IFN in senescent cells and promotes age-associated inflammation

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Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence

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Targeting STING with covalent small-molecule inhibitors

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Cyclic [G(2′,5′)pA(3′,5′)p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase.

Gao, P., Ascano, M., Wu, Y., Barchet, W., Gaffney, B. L., Zillinger, T., Serganov, A. A., Liu, Y., Jones, R. A., Hartmann, G., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.046 · Cited by 1,101 · see citing works

Structural basis of STING binding with and phosphorylation by TBK1

Zhang, C., Shang, G., Gui, X., Zhang, X., Bai, X.-C., & Chen, Z. J. (2019) · Nature · doi:10.1038/s41586-019-1000-2 · Cited by 1,095 · see citing works

Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING

Zhang, X., Shi, H., Wu, J., Zhang, X., Sun, L., Chen, C., & Chen, Z. J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.05.022 · Cited by 1,086 · see citing works

cGAS in action: Expanding roles in immunity and inflammation

Ablasser, A., & Chen, Z. J. (2019) · Science · doi:10.1126/science.aat8657 · Cited by 1,077 · see citing works

BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis

McArthur, K., Whitehead, L. W., Heddleston, J. M., Li, L., Padman, B. S., Oorschot, V., Geoghegan, N. D., Chappaz, S., Davidson, S., San Chin, H., et al. (2018) · Science · doi:10.1126/science.aao6047 · Cited by 1,072 · see citing works

DNA-induced liquid phase condensation of cGAS activates innate immune signaling

Du, M., & Chen, Z. J. (2018) · Science · doi:10.1126/science.aat1022 · Cited by 1,068 · see citing works

TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS

Yu, C.-H., Davidson, S., Harapas, C. R., Hilton, J. B., Mlodzianoski, M. J., Laohamonthonkul, P., Louis, C., Low, R. R. J., Moecking, J., De Nardo, D., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.020 · Cited by 1,019 · see citing works

cGAS is essential for cellular senescence

Yang, H., Wang, H., Ren, J., Chen, Q., & Chen, Z. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705499114 · Cited by 1,009 · see citing works

Recognition of Cytosolic DNA Activates an IRF3-Dependent Innate Immune Response

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Apoptotic Caspases Suppress mtDNA-Induced STING-Mediated Type I IFN Production

White, M. J., McArthur, K., Metcalf, D., Lane, R. M., Cambier, J. C., Herold, M. J., van Delft, M. F., Bedoui, S., Lessene, G., Ritchie, M. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.036 · Cited by 983 · see citing works

Effect of friction on oxidative graphite intercalation and high-quality graphene formation

Seiler, S., Halbig, C. E., Grote, F., Rietsch, P., Börrnert, F., Kaiser, U. A., Meyer, B., & Eigler, S. (2018) · Nature Communications · doi:10.1038/s41467-018-03211-1 · Cited by 971 · see citing works

Carcinoma–astrocyte gap junctions promote brain metastasis by cGAMP transfer

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Aicardi–Goutières syndrome and the type I interferonopathies

Crow, Y. J., & Manel, N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3850 · Cited by 925 · see citing works

Design of amidobenzimidazole STING receptor agonists with systemic activity

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Structural mechanism of cytosolic DNA sensing by cGAS

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Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response

Saitoh, T., Fujita, N., Hayashi, T., Takahara, K., Satoh, T., Lee, H., Matsunaga, K., Kageyama, S., Omori, H., Noda, T., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911267106 · Cited by 854 · see citing works

Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA

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VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease

Kim, J., Gupta, R., Blanco, L. P., Yang, S., Shteinfer-Kuzmine, A., Wang, K., Zhu, J., Yoon, H. E., Wang, X., Kerkhofs, M., et al. (2019) · Science · doi:10.1126/science.aav4011 · Cited by 793 · see citing works

Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP–AMP

Shang, G., Zhang, C., Chen, Z. J., Bai, X., & Zhang, X. (2019) · Nature · doi:10.1038/s41586-019-0998-5 · Cited by 775 · see citing works

The innate immune DNA Sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING.

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Activation of STING requires palmitoylation at the Golgi

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Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus

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DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity

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Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases

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Cyclic Dinucleotides Trigger ULK1 (ATG1) Phosphorylation of STING to Prevent Sustained Innate Immune Signaling

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Cyclic GMP-AMP Synthase Is Activated by Double-Stranded DNA-Induced Oligomerization

Li, X., Shu, C., Yi, G., Chaton, C. T., Shelton, C. L., Diao, J., Zuo, X., Kao, C. C., Herr, A. B., & Li, P. (2013) · Immunity · doi:10.1016/j.immuni.2013.10.019 · Cited by 656 · see citing works

Nuclear cGAS suppresses DNA repair and promotes tumorigenesis

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Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP

Ablasser, A., Schmid-Burgk, J. L., Hemmerling, I., Horvath, G. L., Schmidt, T., Latz, E., & Hornung, V. (2013) · Nature · doi:10.1038/nature12640 · Cited by 649 · see citing works

STING Activation by Translocation from the ER Is Associated with Infection and Autoinflammatory Disease

Dobbs, N., Burnaevskiy, N., Chen, D., Gonugunta, V. K., Alto, N. M., & Yan, N. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.07.001 · Cited by 638 · see citing works

The DNA Inflammasome in Human Myeloid Cells Is Initiated by a STING-Cell Death Program Upstream of NLRP3

Gaidt, M. M., Ebert, T. S., Chauhan, D., Ramshorn, K., Pinci, F., Zuber, S., O’Duill, F., Schmid-Burgk, J. L., Hoss, F., Buhmann, R., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.039 · Cited by 638 · see citing works

Structure-Function Analysis of STING Activation by c[G(2′,5′)pA(3′,5′)p] and Targeting by Antiviral DMXAA

Gao, P., Ascano, M., Zillinger, T., Wang, W., Dai, P., Serganov, A. A., Gaffney, B. L., Shuman, S., Jones, R. A., Deng, L., et al. (2013) · Cell · doi:10.1016/j.cell.2013.07.023 · Cited by 595 · see citing works

T cells with dysfunctional mitochondria induce multimorbidity and premature senescence

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IRF3 and type I interferons fuel a fatal response to myocardial infarction

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Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations

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Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis

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Lysosome-mediated processing of chromatin in senescence

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DNA released from dying host cells mediates aluminum adjuvant activity

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Hydrolysis of 2′3′-cGAMP by ENPP1 and design of nonhydrolyzable analogs

Li, L., Yin, Q., Kuss, P., Maliga, Z., Millán, J. L., Wu, H., & Mitchison, T. J. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1661 · Cited by 537 · see citing works

Cyclic GMP–AMP signalling protects bacteria against viral infection

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STING manifests self DNA-dependent inflammatory disease

Ahn, J., Gutman, D. M., Saijo, S., & Barber, G. N. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215006109 · Cited by 512 · see citing works

cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein-DNA ladders

Andreeva, L., Hiller, B., Kostrewa, D., Lässig, C., de Oliveira Mann, C. C., Jan Drexler, D., Maiser, A., Gaidt, M., Leonhardt, H., Hornung, V., et al. (2017) · Nature · doi:10.1038/nature23890 · Cited by 511 · see citing works

Autoimmunity Initiates in Nonhematopoietic Cells and Progresses via Lymphocytes in an Interferon-Dependent Autoimmune Disease

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The Cytosolic DNA Sensor cGAS Forms an Oligomeric Complex with DNA and Undergoes Switch-like Conformational Changes in the Activation Loop

Zhang, X., Wu, J., Du, F., Xu, H., Sun, L., Chen, Z., Brautigam, C. A., Zhang, X., & Chen, Z. J. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.01.003 · Cited by 507 · see citing works

Signalling strength determines proapoptotic functions of STING

Gulen, M. F., Koch, U., Haag, S. M., Schuler, F., Apetoh, L., Villunger, A., Radtke, F., & Ablasser, A. (2017) · Nature Communications · doi:10.1038/s41467-017-00573-w · Cited by 505 · see citing works

LINE1 Derepression in aged wild-type and SIRT6-deficient mice drives inflammation

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Host STING-dependent MDSC mobilization drives extrinsic radiation resistance

Liang, H. L., Deng, L., Hou, Y., Meng, X., Huang, X., Rao, E., Zheng, W., Mauceri, H. J., Mack, M., Xu, M. M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01566-5 · Cited by 491 · see citing works

TBK1 and IKKε Act Redundantly to Mediate STING-Induced NF-κB Responses in Myeloid Cells

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Limited Mitochondrial Permeabilization Causes DNA Damage and Genomic Instability in the Absence of Cell Death

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Attenuation of cGAS‐STING signaling is mediated by a p62/SQSTM1‐dependent autophagy pathway activated by TBK1

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Oxidative Damage of DNA Confers Resistance to Cytosolic Nuclease TREX1 Degradation and Potentiates STING-Dependent Immune Sensing

Gehrke, N., Mertens, C., Zillinger, T., Wenzel, J., Bald, T., Zahn, S., Tüting, T., Hartmann, G., & Barchet, W. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.004 · Cited by 476 · see citing works

Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages

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STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease

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Inflammation-driven carcinogenesis is mediated through STING

Ahn, J., Xia, T., Konno, H., Konno, K., Ruiz, P., & Barber, G. N. (2014) · Nature Communications · doi:10.1038/ncomms6166 · Cited by 449 · see citing works

A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1

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Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study

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COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis

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The Ca2+ sensor STIM1 regulates the type I interferon response by retaining the signaling adaptor STING at the endoplasmic reticulum

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Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion

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Lethal anemia caused by interferon-β produced in mouse embryos carrying undigested DNA

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An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells

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LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance

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Regulation of cGAS- and RLR-mediated immunity to nucleic acids

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Modeling of TREX1-dependent autoimmune disease using human stem cells highlights L1 accumulation as a source of neuroinflammation

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Interleukin-1β Induces mtDNA Release to Activate Innate Immune Signaling via cGAS-STING

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Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling

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Familial chilblain lupus due to a gain-of-function mutation in STING

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Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes

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Development of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression

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Tight nuclear tethering of cGAS is essential for preventing autoreactivity

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Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity

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Cancer-Cell-Intrinsic cGAS Expression Mediates Tumor Immunogenicity

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cGAS drives noncanonical-inflammasome activation in age-related macular degeneration

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Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort

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STING-dependent sensing of self-DNA drives silica-induced lung inflammation

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Evolutionary Origins of cGAS-STING Signaling

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Cytosolic DNA Sensing Promotes Macrophage Transformation and Governs Myocardial Ischemic Injury

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Non-canonical NF-κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy

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Structural basis for sequestration and autoinhibition of cGAS by chromatin

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Viruses transfer the antiviral second messenger cGAMP between cells

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Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2′,3′ cGAMP Signaling

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Challenges and Opportunities in the Clinical Development of STING Agonists for Cancer Immunotherapy

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Ribonuclease H2 mutations induce a cGAS/STING‐dependent innate immune response

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The N-Terminal Domain of cGAS Determines Preferential Association with Centromeric DNA and Innate Immune Activation in the Nucleus

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RNase H2 catalytic core Aicardi-Goutières syndrome–related mutant invokes cGAS–STING innate immune-sensing pathway in mice

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Cutting Edge: Antimalarial Drugs Inhibit IFN-β Production through Blockade of Cyclic GMP-AMP Synthase–DNA Interaction

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Repetitive Elements in Mammalian Telomeres Suppress Bacterial DNA-Induced Immune Activation

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Structural basis of nucleosome-dependent cGAS inhibition

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Crystal structures of STING protein reveal basis for recognition of cyclic di-GMP

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Type I interferon-mediated autoinflammation due to DNase II deficiency

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STING Signaling Promotes Inflammation in Experimental Acute Pancreatitis

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Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling

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Modular Architecture of the STING C-Terminal Tail Allows Interferon and NF-κB Signaling Adaptation

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The structural basis for the sensing and binding of cyclic di-GMP by STING

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Human cGAS catalytic domain has an additional DNA-binding interface that enhances enzymatic activity and liquid-phase condensation

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BAF restricts cGAS on nuclear DNA to prevent innate immune activation

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STING-associated vasculopathy develops independently of IRF3 in mice

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A defect in COPI-mediated transport of STING causes immune dysregulation in COPA syndrome

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Expression of Cyclic GMP‐AMP Synthase in Patients With Systemic Lupus Erythematosus

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Copa Syndrome: a Novel Autosomal Dominant Immune Dysregulatory Disease

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cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing

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Discovery of a Novel cGAMP Competitive Ligand of the Inactive Form of STING

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Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells

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Intracellular Nucleic Acid Sensing Triggers Necroptosis through Synergistic Type I IFN and TNF Signaling

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STEEP mediates STING ER exit and activation of signaling

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Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by a novel fluorescence polarization assay

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Suppression of systemic autoimmunity by the innate immune adaptor STING

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The Mechanism for Type I Interferon Induction by Mycobacterium tuberculosis is Bacterial Strain-Dependent

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STING-mediated type-I interferons contribute to the neuroinflammatory process and detrimental effects following traumatic brain injury

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Interferon-independent STING signaling promotes resistance to HSV-1 in vivo

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Netting Neutrophils Activate Autoreactive B Cells in Lupus

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Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease

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Cutting Edge: STING Mediates Protection against Colorectal Tumorigenesis by Governing the Magnitude of Intestinal Inflammation

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Beyond DNA binding - a review of the potential mechanisms mediating quinacrine's therapeutic activities in parasitic infections, inflammation, and cancers

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Mitochondrial DNA stress signalling protects the nuclear genome

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Hierarchy of clinical manifestations in SAVI N153S and V154M mouse models

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Suramin Potently Inhibits cGAMP Synthase, cGAS, in THP1 Cells to Modulate IFN-β Levels

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TMEM173 variants and potential importance to human biology and disease

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Antimalarial Drugs as Immune Modulators: New Mechanisms for Old Drugs

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Self-Awareness: Nucleic Acid–Driven Inflammation and the Type I Interferonopathies

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Inhibition of Cyclic GMP ‐ AMP Synthase Using a Novel Antimalarial Drug Derivative in Trex1 ‐Deficient Mice

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Chronic neurodegeneration induces type I interferon synthesis via STING, shaping microglial phenotype and accelerating disease progression

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ALK is a therapeutic target for lethal sepsis

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A Mutation Outside the Dimerization Domain Causing Atypical STING-Associated Vasculopathy With Onset in Infancy

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Pro-inflammation Associated with a Gain-of-Function Mutation (R284S) in the Innate Immune Sensor STING

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Synthetic oligodeoxynucleotides containing suppressive TTAGGG motifs inhibit AIM2 inflammasome activation

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Roles of the cGAS-STING Pathway in Cancer Immunosurveillance and Immunotherapy

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Cytosolic DNA sensor cGAS plays an essential pathogenetic role in pressure overload-induced heart failure

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Severe combined immunodeficiency in stimulator of interferon genes (STING) V154M/wild-type mice

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cGAS and CD-NTase enzymes: structure, mechanism, and evolution

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Discovery of Small-Molecule Cyclic GMP-AMP Synthase Inhibitors

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STING Mediates Lupus via the Activation of Conventional Dendritic Cell Maturation and Plasmacytoid Dendritic Cell Differentiation

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Hepatic gap junctions amplify alcohol liver injury by propagating cGAS-mediated IRF3 activation

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Accumulation of cytosolic dsDNA contributes to fibroblast-like synoviocytes-mediated rheumatoid arthritis synovial inflammation

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A novel STING1 variant causes a recessive form of STING-associated vasculopathy with onset in infancy (SAVI)

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STING and TRIF Contribute to Mouse Sepsis, Depending on Severity of the Disease Model

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The Common R71H-G230A-R293Q Human TMEM173 Is a Null Allele

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In Silico Screening-Based Discovery of Novel Inhibitors of Human Cyclic GMP–AMP Synthase: A Cross-Validation Study of Molecular Docking and Experimental Testing

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Novel TMEM173 Mutation and the Role of Disease Modifying Alleles

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Role of neuroinflammation in neurodegeneration development

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

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Cellular senescence and senolytics: the path to the clinic

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Chronic inflammation and the hallmarks of aging

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Tumor microenvironment signaling and therapeutics in cancer progression

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Activation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5×FAD mice

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Cytoplasmic DNA: sources, sensing, and role in aging and disease

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STING mediates neurodegeneration and neuroinflammation in nigrostriatal α-synucleinopathy

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Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders

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COVID-19 and cellular senescence

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Mitophagy and cGAS–STING crosstalk in neuroinflammation

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Blockade of STING Activation Alleviates Microglial Dysfunction and a Broad Spectrum of Alzheimer's Disease Pathologies

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Constitutively active STING causes neuroinflammation and degeneration of dopaminergic neurons in mice

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Immunopathogenic mechanisms and immunoregulatory therapies in MASLD

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Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway

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Microglia in Alzheimer's Disease: a Key Player in the Transition Between Homeostasis and Pathogenesis

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Alpha-synuclein–mediated DNA damage, STING activation, and neuroinflammation in Parkinson’s disease

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High Concentration Hydrogen Protects Sepsis‐Associated Encephalopathy by Enhancing Pink1/Parkin‐Mediated Mitophagy and Inhibiting <scp>cGAS</scp> ‐ <scp>STING</scp> ‐ <scp>IRF3</scp> Pathway

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Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation

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Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery

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Prolonged activation of innate immune pathways by a polyvalent STING agonist

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STING inhibitors target the cyclic dinucleotide binding pocket

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Taking the STING out of cytosolic DNA sensing

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