Pathophysiological functions of self-derived DNA

References

• Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015;33:257–290. doi:10.1146/annurev-immunol-032414-112240.
   PubMed Web of Science ®Google Scholar
• Okude H, Ori D, Kawai T. Signaling through nucleic acid sensors and their roles in inflammatory diseases. Front Immunol. 2020;11:625833.
   PubMed Web of Science ®Google Scholar
• Kawasaki T, Kawai T, Akira S. Recognition of nucleic acids by pattern-recognition receptors and its relevance in autoimmunity. Immunol Rev. 2011;243(1):61–73. doi:10.1111/j.1600-065X.2011.01048.x.
   PubMedGoogle Scholar
• Hemmi H, Takeuchi O, Kawai T, et al. A Toll-like receptor recognizes bacterial DNA. Nature. 2000;408(6813):740–745. doi:10.1038/35047123.
   PubMed Web of Science ®Google Scholar
• Lee BL, Barton GM. Trafficking of endosomal Toll-like receptors. Trends Cell Biol. 2014;24(6):360–369. doi:10.1016/j.tcb.2013.12.002.
   PubMed Web of Science ®Google Scholar
• Barton GM, Kagan JC, Medzhitov R. Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol. 2006;7(1):49–56. doi:10.1038/ni1280.
   PubMed Web of Science ®Google Scholar
• Kim YM, Brinkmann MM, Paquet ME, Ploegh HL. UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature. 2008;452(7184):234–238. doi:10.1038/nature06726.
   PubMed Web of Science ®Google Scholar
• Tabeta K, Hoebe K, Janssen EM, et al. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nat Immunol. 2006;7(2):156–164. doi:10.1038/ni1297.
   PubMed Web of Science ®Google Scholar
• Pelka K, Bertheloot D, Reimer E, et al. The chaperone UNC93B1 regulates toll-like receptor stability independently of endosomal TLR transport. Immunity. 2018;48(5):911–922 e917. doi:10.1016/j.immuni.2018.04.011.
   PubMed Web of Science ®Google Scholar
• Majer O, Liu B, Woo BJ, Kreuk LSM, Van Dis E, Barton GM. Release from UNC93B1 reinforces the compartmentalized activation of select TLRs. Nature. 2019;575(7782):371–374. doi:10.1038/s41586-019-1611-7.
   PubMed Web of Science ®Google Scholar
• Ewald SE, Engel A, Lee J, Wang M, Bogyo M, Barton GM. Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J Exp Med. 2011;208(4):643–651. doi:10.1084/jem.20100682.
   PubMed Web of Science ®Google Scholar
• Garcia-Cattaneo A, Gobert FX, Muller M, et al. Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for signaling. Proc Natl Acad Sci USA. 2012;109(23):9053–9058. doi:10.1073/pnas.1115091109.
   PubMed Web of Science ®Google Scholar
• Mouchess ML, Arpaia N, Souza G, et al. Transmembrane mutations in Toll-like receptor 9 bypass the requirement for ectodomain proteolysis and induce fatal inflammation. Immunity. 2011;35(5):721–732. doi:10.1016/j.immuni.2011.10.009.
   PubMed Web of Science ®Google Scholar
• Hacker H, Mischak H, Miethke T, et al. CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J. 1998;17(21):6230–6240. doi:10.1093/emboj/17.21.6230.
   PubMed Web of Science ®Google Scholar
• Murase M, Kawasaki T, Hakozaki R, et al. Intravesicular acidification regulates lipopolysaccharide inflammation and tolerance through TLR4 trafficking. J Immunol. 2018;200(8):2798–2808. doi:10.4049/jimmunol.1701390.
   PubMed Web of Science ®Google Scholar
• Sasai M, Linehan MM, Iwasaki A. Bifurcation of toll-like receptor 9 signaling by adaptor protein 3. Science. 2010;329(5998):1530–1534. doi:10.1126/science.1187029.
   PubMed Web of Science ®Google Scholar
• Ohto U, Shibata T, Tanji H, et al. Structural basis of CpG and inhibitory DNA recognition by toll-like receptor 9. Nature. 2015;520(7549):702–705. doi:10.1038/nature14138.
   PubMed Web of Science ®Google Scholar
• Ohto U, Ishida H, Shibata T, Sato R, Miyake K, Shimizu T. Toll-like receptor 9 contains two DNA binding sites that function cooperatively to promote receptor dimerization and activation. Immunity. 2018;48(4):649–658 e644. doi:10.1016/j.immuni.2018.03.013.
   PubMed Web of Science ®Google Scholar
• Ori D, Murase M, Kawai T. Cytosolic nucleic acid sensors and innate immune regulation. Int Rev Immunol. 2017;36(2):74–88. doi:10.1080/08830185.2017.1298749.
   PubMed Web of Science ®Google Scholar
• Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 2009;138(3):576–591. doi:10.1016/j.cell.2009.06.015.
   PubMed Web of Science ®Google Scholar
• Kondo T, Kobayashi J, Saitoh T, et al. DNA damage sensor MRE11 recognizes cytosolic double-stranded DNA and induces type I interferon by regulating STING trafficking. Proc Natl Acad Sci USA. 2013;110(8):2969–2974. doi:10.1073/pnas.1222694110.
   PubMed Web of Science ®Google Scholar
• Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013;339(6121):786–791. doi:10.1126/science.1232458.
   PubMed Web of Science ®Google Scholar
• Takaoka A, Wang Z, Choi MK, et al. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature. 2007;448(7152):501–505. doi:10.1038/nature06013.
   PubMed Web of Science ®Google Scholar
• Unterholzner L, Keating SE, Baran M, et al. IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol. 2010;11(11):997–1004. doi:10.1038/ni.1932.
   PubMed Web of Science ®Google Scholar
• Li X, Shu C, Yi G, et al. Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization. Immunity. 2013;39(6):1019–1031. doi:10.1016/j.immuni.2013.10.019.
   PubMed Web of Science ®Google Scholar
• Zhang X, Wu J, Du F, et al. The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop. Cell Rep. 2014;6(3):421–430. doi:10.1016/j.celrep.2014.01.003.
   PubMed Web of Science ®Google Scholar
• Andreeva L, Hiller B, Kostrewa D, et al. cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein-DNA ladders. Nature. 2017;549(7672):394–398. doi:10.1038/nature23890.
   PubMed Web of Science ®Google Scholar
• Hooy RM, Sohn J. The allosteric activation of cGAS underpins its dynamic signaling landscape. Elife. 2018;7:e39984. doi:10.7554/eLife.39984.
   PubMed Web of Science ®Google Scholar
• Luecke S, Holleufer A, Christensen MH, et al. cGAS is activated by DNA in a length-dependent manner. EMBO Rep. 2017;18(10):1707–1715. doi:10.15252/embr.201744017.
   PubMed Web of Science ®Google Scholar
• Barnett KC, Coronas-Serna JM, Zhou W, et al. Phosphoinositide interactions position cGAS at the plasma membrane to ensure efficient distinction between self- and viral DNA. Cell. 2019;176(6):1432–1446 e1411. doi:10.1016/j.cell.2019.01.049.
   PubMed Web of Science ®Google Scholar
• Gentili M, Lahaye X, Nadalin F, et al. The N-terminal domain of cGAS determines preferential association with centromeric DNA and innate immune activation in the nucleus. Cell Rep. 2019;26(13):3798. doi:10.1016/j.celrep.2019.03.049.
   PubMed Web of Science ®Google Scholar
• Jiang H, Xue X, Panda S, et al. Chromatin-bound cGAS is an inhibitor of DNA repair and hence accelerates genome destabilization and cell death. EMBO J. 2019;38(21):e102718. doi:10.15252/embj.2019102718.
   PubMed Web of Science ®Google Scholar
• Boyer JA, Spangler CJ, Strauss JD, et al. Structural basis of nucleosome-dependent cGAS inhibition. Science. 2020;370(6515):450–454. doi:10.1126/science.abd0609.
   PubMed Web of Science ®Google Scholar
• Cao D, Han X, Fan X, Xu RM, Zhang X. Structural basis for nucleosome-mediated inhibition of cGAS activity. Cell Res. 2020;30(12):1088–1097. doi:10.1038/s41422-020-00422-4.
   PubMed Web of Science ®Google Scholar
• Kujirai T, Zierhut C, Takizawa Y, et al. Structural basis for the inhibition of cGAS by nucleosomes. Science. 2020;370(6515):455–458. doi:10.1126/science.abd0237.
   PubMed Web of Science ®Google Scholar
• Pathare GR, Decout A, Gluck S, et al. Structural mechanism of cGAS inhibition by the nucleosome. Nature. 2020;587(7835):668–672. doi:10.1038/s41586-020-2750-6.
   PubMed Web of Science ®Google Scholar
• Zhao B, Xu P, Rowlett CM, et al. The molecular basis of tight nuclear tethering and inactivation of cGAS. Nature. 2020;587(7835):673–677. doi:10.1038/s41586-020-2749-z.
   PubMed Web of Science ®Google Scholar
• Shang G, Zhang C, Chen ZJ, Bai XC, Zhang X. Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP. Nature. 2019;567(7748):389–393. doi:10.1038/s41586-019-0998-5.
   PubMed Web of Science ®Google Scholar
• Zhang C, Shang G, Gui X, Zhang X, Bai XC, Chen ZJ. Structural basis of STING binding with and phosphorylation by TBK1. Nature. 2019;567(7748):394–398. doi:10.1038/s41586-019-1000-2.
   PubMed Web of Science ®Google Scholar
• Ritchie C, Cordova AF, Hess GT, Bassik MC, Li L. SLC19A1 is an importer of the immunotransmitter cGAMP. Mol Cell. 2019;75(2):372–381 e375. doi:10.1016/j.molcel.2019.05.006.
   PubMed Web of Science ®Google Scholar
• Schadt L, Sparano C, Schweiger NA, et al. Cancer-cell-intrinsic cGAS expression mediates tumor immunogenicity. Cell Rep. 2019;29(5):1236–1248 e1237. doi:10.1016/j.celrep.2019.09.065.
   PubMed Web of Science ®Google Scholar
• Ablasser A, Schmid-Burgk JL, Hemmerling I, et al. Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. Nature. 2013;503(7477):530–534. doi:10.1038/nature12640.
   PubMed Web of Science ®Google Scholar
• Zhou C, Chen X, Planells-Cases R, et al. Transfer of cGAMP into bystander cells via LRRC8 volume-regulated anion channels augments STING-mediated interferon responses and anti-viral immunity. Immunity. 2020;52(5):767–781 e766. doi:10.1016/j.immuni.2020.03.016.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Fei M, Zhang G, et al. Blockade of the phagocytic receptor MerTK on tumor-associated macrophages enhances P2X7R-dependent STING activation by tumor-derived cGAMP. Immunity. 2020;52(2):357–373 e359. doi:10.1016/j.immuni.2020.01.014.
   PubMed Web of Science ®Google Scholar
• Bridgeman A, Maelfait J, Davenne T, et al. Viruses transfer the antiviral second messenger cGAMP between cells. Science. 2015;349(6253):1228–1232. doi:10.1126/science.aab3632.
   PubMed Web of Science ®Google Scholar
• Gentili M, Kowal J, Tkach M, et al. Transmission of innate immune signaling by packaging of cGAMP in viral particles. Science. 2015;349(6253):1232–1236. doi:10.1126/science.aab3628.
   PubMed Web of Science ®Google Scholar
• Dobbs N, Burnaevskiy N, Chen D, Gonugunta VK, Alto NM, Yan N. STING activation by translocation from the ER is associated with infection and autoinflammatory disease. Cell Host Microbe. 2015;18(2):157–168. doi:10.1016/j.chom.2015.07.001.
   PubMed Web of Science ®Google Scholar
• Srikanth S, Woo JS, Wu B, et al. The Ca2+ sensor STIM1 regulates the type I interferon response by retaining the signaling adaptor STING at the endoplasmic reticulum. Nat Immunol. 2019;20(2):152–162. doi:10.1038/s41590-018-0287-8.
   PubMed Web of Science ®Google Scholar
• Pokatayev V, Yang K, Tu X, et al. Homeostatic regulation of STING protein at the resting state by stabilizer TOLLIP. Nat Immunol. 2020;21(2):158–167. doi:10.1038/s41590-019-0569-9.
   PubMed Web of Science ®Google Scholar
• Zhang BC, Nandakumar R, Reinert LS, et al. STEEP mediates STING ER exit and activation of signaling. Nat Immunol. 2020;21(8):868–879. doi:10.1038/s41590-020-0730-5.
   PubMed Web of Science ®Google Scholar
• Dewi Pamungkas Putri D, Kawasaki T, Murase M, et al. PtdIns3P phosphatases MTMR3 and MTMR4 negatively regulate innate immune responses to DNA through modulating STING trafficking. J Biol Chem. 2019;294(21):8412–8423. doi:10.1074/jbc.RA118.005731.
   PubMed Web of Science ®Google Scholar
• Tsuchida T, Zou J, Saitoh T, et al. The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity. 2010;33(5):765–776. doi:10.1016/j.immuni.2010.10.013.
   PubMed Web of Science ®Google Scholar
• Yang L, Wang L, Ketkar H, et al. UBXN3B positively regulates STING-mediated antiviral immune responses. Nat Commun. 2018;9(1):2329. doi:10.1038/s41467-018-04759-8.
   PubMedGoogle Scholar
• Cheng Z, Dai T, He X, et al. The interactions between cGAS-STING pathway and pathogens. Signal Transduct Target Ther. 2020;5(1):91.
   PubMed Web of Science ®Google Scholar
• Mukai K, Konno H, Akiba T, et al. Activation of STING requires palmitoylation at the Golgi. Nat Commun. 2016;7:11932. doi:10.1038/ncomms11932.
   PubMed Web of Science ®Google Scholar
• Liu S, Cai X, Wu J, et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science. 2015;347(6227):aaa2630. doi:10.1126/science.aaa2630.
   PubMed Web of Science ®Google Scholar
• Zhao B, Du F, Xu P, et al. A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1. Nature. 2019;569(7758):718–722. doi:10.1038/s41586-019-1228-x.
   PubMed Web of Science ®Google Scholar
• Takahama M, Fukuda M, Ohbayashi N, et al. The RAB2B-GARIL5 complex promotes cytosolic DNA-induced innate immune responses. Cell Rep. 2017;20(12):2944–2954. doi:10.1016/j.celrep.2017.08.085.
   PubMed Web of Science ®Google Scholar
• Gui X, Yang H, Li T, et al. Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature. 2019;567(7747):262–266. doi:10.1038/s41586-019-1006-9.
   PubMed Web of Science ®Google Scholar
• Ma Z, Damania B. The cGAS-STING defense pathway and its counteraction by viruses. Cell Host Microbe. 2016;19(2):150–158. doi:10.1016/j.chom.2016.01.010.
   PubMed Web of Science ®Google Scholar
• Gao D, Wu J, Wu YT, et al. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science. 2013;341(6148):903–906. doi:10.1126/science.1240933.
   PubMed Web of Science ®Google Scholar
• Andrade WA, Agarwal S, Mo S, et al. Type I interferon induction by Neisseria gonorrhoeae: dual requirement of cyclic GMP-AMP synthase and toll-like receptor 4. Cell Rep. 2016;15(11):2438–2448. doi:10.1016/j.celrep.2016.05.030.
   PubMed Web of Science ®Google Scholar
• Hansen K, Prabakaran T, Laustsen A, et al. Listeria monocytogenes induces IFNβ expression through an IFI16-, cGAS- and STING-dependent pathway. EMBO J. 2014;33(15):1654–1666. doi:10.15252/embj.201488029.
   PubMed Web of Science ®Google Scholar
• Wiens KE, Ernst JD. The mechanism for type I interferon induction by Mycobacterium tuberculosis is bacterial strain-dependent. PLoS Pathog. 2016;12(8):e1005809. doi:10.1371/journal.ppat.1005809.
   PubMed Web of Science ®Google Scholar
• Ku JWK, Chen Y, Lim BJW, Gasser S, Crasta KC, Gan YH. Bacterial-induced cell fusion is a danger signal triggering cGAS-STING pathway via micronuclei formation. Proc Natl Acad Sci USA. 2020;117(27):15923–15934. doi:10.1073/pnas.2006908117.
   PubMed Web of Science ®Google Scholar
• Ning X, Wang Y, Jing M, et al. Apoptotic caspases suppress type I interferon production via the cleavage of cGAS, MAVS, and IRF3. Mol Cell. 2019;74(1):19–31 e17. doi:10.1016/j.molcel.2019.02.013.
   PubMed Web of Science ®Google Scholar
• Rongvaux A, Jackson R, Harman CC, et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell. 2014;159(7):1563–1577. doi:10.1016/j.cell.2014.11.037.
   PubMed Web of Science ®Google Scholar
• White MJ, McArthur K, Metcalf D, et al. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell. 2014;159(7):1549–1562. doi:10.1016/j.cell.2014.11.036.
   PubMed Web of Science ®Google Scholar
• Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol. 2016;16(7):407–420. doi:10.1038/nri.2016.58.
   PubMed Web of Science ®Google Scholar
• Gaidt MM, Ebert TS, Chauhan D, et al. The DNA inflammasome in human myeloid cells is initiated by a STING-cell death program upstream of NLRP3. Cell. 2017;171(5):1110–1124 e1118. doi:10.1016/j.cell.2017.09.039.
   PubMed Web of Science ®Google Scholar
• Swanson KV, Junkins RD, Kurkjian CJ, et al. A noncanonical function of cGAMP in inflammasome priming and activation. J Exp Med. 2017;214(12):3611–3626. doi:10.1084/jem.20171749.
   PubMed Web of Science ®Google Scholar
• Wang W, Hu D, Wu C, et al. STING promotes NLRP3 localization in ER and facilitates NLRP3 deubiquitination to activate the inflammasome upon HSV-1 infection. PLoS Pathog. 2020;16(3):e1008335. doi:10.1371/journal.ppat.1008335.
   PubMed Web of Science ®Google Scholar
• Man SM, Karki R, Kanneganti TD. AIM2 inflammasome in infection, cancer, and autoimmunity: role in DNA sensing, inflammation, and innate immunity. Eur J Immunol. 2016;46(2):269–280. doi:10.1002/eji.201545839.
   PubMed Web of Science ®Google Scholar
• Rathinam VA, Jiang Z, Waggoner SN, et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol. 2010;11(5):395–402. doi:10.1038/ni.1864.
   PubMed Web of Science ®Google Scholar
• Reinholz M, Kawakami Y, Salzer S, et al. HPV16 activates the AIM2 inflammasome in keratinocytes. Arch Dermatol Res. 2013;305(8):723–732. doi:10.1007/s00403-013-1375-0.
   PubMed Web of Science ®Google Scholar
• Moriyama M, Nagai M, Maruzuru Y, Koshiba T, Kawaguchi Y, Ichinohe T. Influenza virus-induced oxidized DNA activates inflammasomes. iScience. 2020;23(7):101270. doi:10.1016/j.isci.2020.101270.
   PubMed Web of Science ®Google Scholar
• Schattgen SA, Gao G, Kurt-Jones EA, Fitzgerald KA. Cutting edge: DNA in the lung microenvironment during influenza virus infection tempers inflammation by engaging the DNA sensor AIM2. J Immunol. 2016;196(1):29–33. doi:10.4049/jimmunol.1501048.
   PubMed Web of Science ®Google Scholar
• Zhang H, Luo J, Alcorn JF, et al. AIM2 inflammasome is critical for influenza-induced lung injury and mortality. J Immunol. 2017;198(11):4383–4393. doi:10.4049/jimmunol.1600714.
   PubMed Web of Science ®Google Scholar
• Almine JF, O’Hare CA, Dunphy G, et al. IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes. Nat Commun. 2017;8:14392. doi:10.1038/ncomms14392.
   PubMed Web of Science ®Google Scholar
• Jonsson KL, Laustsen A, Krapp C, et al. IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP. Nat Commun. 2017;8:14391. doi:10.1038/ncomms14391.
   PubMed Web of Science ®Google Scholar
• Kerur N, Veettil MV, Sharma-Walia N, et al. IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection. Cell Host Microbe. 2011;9(5):363–375. doi:10.1016/j.chom.2011.04.008.
   PubMed Web of Science ®Google Scholar
• Li D, Wu R, Guo W, et al. STING-mediated IFI16 degradation negatively controls type I interferon production. Cell Rep. 2019;29(5):1249–1260 e1244. doi:10.1016/j.celrep.2019.09.069.
   PubMed Web of Science ®Google Scholar
• Dutta D, Dutta S, Veettil MV, et al. BRCA1 regulates IFI16 mediated nuclear innate sensing of herpes viral DNA and subsequent induction of the innate inflammasome and interferon-β responses. PLoS Pathog. 2015;11(6):e1005030. doi:10.1371/journal.ppat.1005030.
   PubMed Web of Science ®Google Scholar
• Karin M, Clevers H. Reparative inflammation takes charge of tissue regeneration. Nature. 2016;529(7586):307–315. doi:10.1038/nature17039.
   PubMed Web of Science ®Google Scholar
• Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013;13(6):397–411. doi:10.1038/nri3452.
   PubMed Web of Science ®Google Scholar
• Gross O, Thomas CJ, Guarda G, Tschopp J. The inflammasome: an integrated view. Immunol Rev. 2011;243(1):136–151. doi:10.1111/j.1600-065X.2011.01046.x.
   PubMed Web of Science ®Google Scholar
• Nakahira K, Haspel JA, Rathinam VA, et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol. 2011;12(3):222–230. doi:10.1038/ni.1980.
   PubMed Web of Science ®Google Scholar
• Ichinohe T, Pang IK, Iwasaki A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol. 2010;11(5):404–410. doi:10.1038/ni.1861.
   PubMed Web of Science ®Google Scholar
• Moriyama M, Koshiba T, Ichinohe T. Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses. Nat Commun. 2019;10(1):4624. doi:10.1038/s41467-019-12632-5.
   PubMed Web of Science ®Google Scholar
• Papadimitraki ED, Choulaki C, Koutala E, et al. Expansion of toll-like receptor 9-expressing B cells in active systemic lupus erythematosus: implications for the induction and maintenance of the autoimmune process. Arthritis Rheum. 2006;54(11):3601–3611. doi:10.1002/art.22197.
   PubMedGoogle Scholar
• Liu Y, Jesus AA, Marrero B, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014;371(6):507–518. doi:10.1056/NEJMoa1312625.
   PubMed Web of Science ®Google Scholar
• Patel S, Jin L. TMEM173 variants and potential importance to human biology and disease. Genes Immun. 2019;20(1):82–89. doi:10.1038/s41435-018-0029-9.
   PubMed Web of Science ®Google Scholar
• Jeremiah N, Neven B, Gentili M, et al. Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Invest. 2014;124(12):5516–5520. doi:10.1172/JCI79100.
   PubMed Web of Science ®Google Scholar
• McCauley ME, O’Rourke JG, Yanez A, et al. C9orf72 in myeloid cells suppresses STING-induced inflammation. Nature. 2020;585(7823):96–101. doi:10.1038/s41586-020-2625-x.
   PubMed Web of Science ®Google Scholar
• Mukai K, Ogawa E, Uematsu R, et al. Homeostatic regulation of STING by retrograde membrane traffic to the ER. Nat Commun. 2021;12(1):61. doi:10.1038/s41467-020-20234-9.
   PubMed Web of Science ®Google Scholar
• Watkin LB, Jessen B, Wiszniewski W, et al. COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis. Nat Genet. 2015;47(6):654–660. doi:10.1038/ng.3279.
   PubMed Web of Science ®Google Scholar
• Kato T, Yamamoto M, Honda Y, et al. Augmentation of stimulator of interferon genes-induced type I interferon production in COPA syndrome. Arthritis Rheumatol. 2021;73(11):2105–2115. doi:10.1002/art.41790.
   PubMed Web of Science ®Google Scholar
• Deng Z, Chong Z, Law CS, et al. A defect in COPI-mediated transport of STING causes immune dysregulation in COPA syndrome. J Exp Med. 2020;217:e20201045. doi:10.1084/jem.20201045.
   PubMed Web of Science ®Google Scholar
• Crow YJ, Chase DS, Lowenstein SJ, et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A. 2015;167A(2):296–312. doi:10.1002/ajmg.a.36887.
   PubMed Web of Science ®Google Scholar
• Al-Mayouf SM, Sunker A, Abdwani R, et al. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat Genet. 2011;43(12):1186–1188. doi:10.1038/ng.975.
   PubMed Web of Science ®Google Scholar
• Kawane K, Ohtani M, Miwa K, et al. Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature. 2006;443(7114):998–1002. doi:10.1038/nature05245.
   PubMed Web of Science ®Google Scholar
• Crow YJ, Hayward BE, Parmar R, et al. Mutations in the gene encoding the 3’-5’ DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. Nat Genet. 2006;38(8):917–920. doi:10.1038/ng1845.
   PubMed Web of Science ®Google Scholar
• Rice GI, Rodero MP, Crow YJ. Human disease phenotypes associated with mutations in TREX1. J Clin Immunol. 2015;35(3):235–243. doi:10.1007/s10875-015-0147-3.
   PubMed Web of Science ®Google Scholar
• Stetson DB, Ko JS, Heidmann T, Medzhitov R. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell. 2008;134(4):587–598. doi:10.1016/j.cell.2008.06.032.
   PubMed Web of Science ®Google Scholar
• Coquel F, Silva MJ, Techer H, et al. SAMHD1 acts at stalled replication forks to prevent interferon induction. Nature. 2018;557(7703):57–61. doi:10.1038/s41586-018-0050-1.
   PubMed Web of Science ®Google Scholar
• Kretschmer S, Wolf C, Konig N, et al. SAMHD1 prevents autoimmunity by maintaining genome stability. Ann Rheum Dis. 2015;74(3):e17. doi:10.1136/annrheumdis-2013-204845.
   PubMed Web of Science ®Google Scholar
• Gray EE, Treuting PM, Woodward JJ, Stetson DB. Cutting edge: cGAS is required for lethal autoimmune disease in the trex1-deficient mouse model of aicardi-goutières syndrome. J Immunol. 2015;195(5):1939–1943. doi:10.4049/jimmunol.1500969.
   PubMed Web of Science ®Google Scholar
• Pokatayev V, Hasin N, Chon H, et al. RNase H2 catalytic core Aicardi-Goutières syndrome-related mutant invokes cGAS-STING innate immune-sensing pathway in mice. J Exp Med. 2016;213(3):329–336. doi:10.1084/jem.20151464.
   PubMed Web of Science ®Google Scholar
• Kisurina-Evgenieva OP, Sutiagina OI, Onishchenko GE. Biogenesis of Micronuclei. Biochemistry (Mosc). 2016;81(5):453–464. doi:10.1134/S0006297916050035.
   PubMed Web of Science ®Google Scholar
• Mackenzie KJ, Carroll P, Martin CA, et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature. 2017;548(7668):461–465. doi:10.1038/nature23449.
   PubMed Web of Science ®Google Scholar
• Harding SM, Benci JL, Irianto J, Discher DE, Minn AJ, Greenberg RA. Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature. 2017;548(7668):466–470. doi:10.1038/nature23470.
   PubMed Web of Science ®Google Scholar
• Bartsch K, Knittler K, Borowski C, et al. Absence of RNase H2 triggers generation of immunogenic micronuclei removed by autophagy. Hum Mol Genet. 2017;26(20):3960–3972. doi:10.1093/hmg/ddx283.
   PubMed Web of Science ®Google Scholar
• Serpas L, Chan RWY, Jiang P, et al. Dnase1l3 deletion causes aberrations in length and end-motif frequencies in plasma DNA. Proc Natl Acad Sci USA. 2019;116(2):641–649. doi:10.1073/pnas.1815031116.
   PubMed Web of Science ®Google Scholar
• Sisirak V, Sally B, D’Agati V, et al. Digestion of chromatin in apoptotic cell microparticles prevents autoimmunity. Cell. 2016;166(1):88–101. doi:10.1016/j.cell.2016.05.034.
   PubMed Web of Science ®Google Scholar
• Soni C, Perez OA, Voss WN, et al. Plasmacytoid dendritic cells and type I interferon promote extrafollicular B cell responses to extracellular self-DNA. Immunity. 2020;52(6):1022–1038 e1027. doi:10.1016/j.immuni.2020.04.015.
   PubMed Web of Science ®Google Scholar
• Kawane K, Fukuyama H, Kondoh G, et al. Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science. 2001;292(5521):1546–1549. doi:10.1126/science.292.5521.1546.
   PubMed Web of Science ®Google Scholar
• Kawane K, Fukuyama H, Yoshida H, et al. Impaired thymic development in mouse embryos deficient in apoptotic DNA degradation. Nat Immunol. 2003;4(2):138–144. doi:10.1038/ni881.
   PubMed Web of Science ®Google Scholar
• Yoshida H, Okabe Y, Kawane K, Fukuyama H, Nagata S. Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA. Nat Immunol. 2005;6(1):49–56. doi:10.1038/ni1146.
   PubMed Web of Science ®Google Scholar
• Kawane K, Tanaka H, Kitahara Y, Shimaoka S, Nagata S. Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation. Proc Natl Acad Sci USA. 2010;107(45):19432–19437. doi:10.1073/pnas.1010603107.
   PubMed Web of Science ®Google Scholar
• Sliter DA, Martinez J, Hao L, et al. Parkin and PINK1 mitigate STING-induced inflammation. Nature. 2018;561(7722):258–262. doi:10.1038/s41586-018-0448-9.
   PubMed Web of Science ®Google Scholar
• Sharma M, Rajendrarao S, Shahani N, Ramirez-Jarquin UN, Subramaniam S. Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease. Proc Natl Acad Sci USA. 2020;117(27):15989–15999. doi:10.1073/pnas.2002144117.
   PubMed Web of Science ®Google Scholar
• Therianou A, Vasiadi M, Delivanis DA, et al. Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis. Exp Dermatol. 2019;28(1):72–75. doi:10.1111/exd.13831.
   PubMed Web of Science ®Google Scholar
• Beranek M, Fiala Z, Kremlacek J, et al. Changes in circulating cell-free DNA and nucleosomes in patients with exacerbated psoriasis. Arch Dermatol Res. 2017;309(10):815–821. doi:10.1007/s00403-017-1785-5.
   PubMed Web of Science ®Google Scholar
• Lande R, Gregorio J, Facchinetti V, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449(7162):564–569. doi:10.1038/nature06116.
   PubMed Web of Science ®Google Scholar
• Liang H, Yan Y, Wu J, et al. Topical nanoparticles interfering with the DNA-LL37 complex to alleviate psoriatic inflammation in mice and monkeys. Sci Adv. 2020;6(31):eabb5274.
   PubMed Web of Science ®Google Scholar
• Bae JH, Jo SI, Kim SJ, et al. Circulating cell-free mtDNA contributes to AIM2 inflammasome-mediated chronic inflammation in patients with type 2 diabetes. Cells. 2019;8(4):328. doi:10.3390/cells8040328.
   PubMed Web of Science ®Google Scholar
• Lam LKM, Murphy S, Kokkinaki D, et al. DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia. Sci Transl Med. 2021;13(616):eabj1008.
   PubMed Web of Science ®Google Scholar
• Xian H, Liu Y, Rundberg Nilsson A, et al. Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation. Immunity. 2021;54(7):1463–1477 e1411. doi:10.1016/j.immuni.2021.05.004.
   PubMed Web of Science ®Google Scholar
• Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nat Rev Immunol. 2013;13(12):875–887. doi:10.1038/nri3547.
   PubMed Web of Science ®Google Scholar
• Gorgoulis V, Adams PD, Alimonti A, et al. Cellular senescence: defining a path forward. Cell. 2019;179(4):813–827. doi:10.1016/j.cell.2019.10.005.
   PubMed Web of Science ®Google Scholar
• McHugh D, Gil J. Senescence and aging: causes, consequences, and therapeutic avenues. J Cell Biol. 2018;217(1):65–77. doi:10.1083/jcb.201708092.
   PubMed Web of Science ®Google Scholar
• Franceschi C, Capri M, Monti D, et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev. 2007;128(1):92–105. doi:10.1016/j.mad.2006.11.016.
   PubMed Web of Science ®Google Scholar
• Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–1217. doi:10.1016/j.cell.2013.05.039.
   PubMed Web of Science ®Google Scholar
• Takahashi A, Loo TM, Okada R, et al. Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells. Nat Commun. 2018;9(1):1249. doi:10.1038/s41467-018-03555-8.
   PubMedGoogle Scholar
• Dou Z, Ghosh K, Vizioli MG, et al. Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature. 2017;550(7676):402–406. doi:10.1038/nature24050.
   PubMed Web of Science ®Google Scholar
• Gluck S, Guey B, Gulen MF, et al. Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence. Nat Cell Biol. 2017;19(9):1061–1070. doi:10.1038/ncb3586.
   PubMed Web of Science ®Google Scholar
• Yang H, Wang H, Ren J, Chen Q, Chen ZJ. cGAS is essential for cellular senescence. Proc Natl Acad Sci USA. 2017;114(23):E4612–E4620.
   PubMed Web of Science ®Google Scholar
• Iske J, Seyda M, Heinbokel T, et al. Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation. Nat Commun. 2020;11(1):4289. doi:10.1038/s41467-020-18039-x.
   PubMed Web of Science ®Google Scholar
• Childs BG, Baker DJ, Wijshake T, Conover CA, Campisi J, van Deursen JM. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science. 2016;354(6311):472–477. doi:10.1126/science.aaf6659.
   PubMed Web of Science ®Google Scholar
• Ogrodnik M, Miwa S, Tchkonia T, et al. Cellular senescence drives age-dependent hepatic steatosis. Nat Commun. 2017;8:15691. doi:10.1038/ncomms15691.
   PubMed Web of Science ®Google Scholar
• Schafer MJ, White TA, Iijima K, et al. Cellular senescence mediates fibrotic pulmonary disease. Nat Commun. 2017;8:14532. doi:10.1038/ncomms14532.
   PubMed Web of Science ®Google Scholar
• Xu M, Pirtskhalava T, Farr JN, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24(8):1246–1256. doi:10.1038/s41591-018-0092-9.
   PubMed Web of Science ®Google Scholar
• Kitai Y, Kawasaki T, Sueyoshi T, et al. DNA-containing exosomes derived from cancer cells treated with topotecan activate a STING-dependent pathway and reinforce antitumor immunity. J Immunol. 2017;198(4):1649–1659. doi:10.4049/jimmunol.1601694.
   PubMed Web of Science ®Google Scholar