{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:19:54Z","timestamp":1788484794857,"version":"build-2803163510"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004156","name":"Mahidol University","doi-asserted-by":"publisher","award":["Basic Research Fund: the fiscal year 2022"],"award-info":[{"award-number":["Basic Research Fund: the fiscal year 2022"]}],"id":[{"id":"10.13039\/501100004156","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chulalongkorn University Graduate Scholarship to commemorate the 72nd Anniversary of His Majesty King Bhumibol Adulyadej"},{"name":"European Research Council"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The absence of stimulator of interferon genes (STING) in 129.B6.<jats:italic>Fcgr2b<\/jats:italic>-deficient mice rescue lupus phenotypes. The administration of a STING inhibitor (ISD017) into the young 129.B6.<jats:italic>Fcgr2b<\/jats:italic>-deficient mice prevents lupus nephritis development. This study mainly aimed to evaluate the effects of STING inhibition (ISD107) on established SLE in mice to prove that ISD017 could be a good therapeutic drug to reverse the already set-up autoimmunity and kidney impairment. Twenty-four-week-old <jats:italic>Fcgr2b<\/jats:italic>-deficient mice were treated with cyclophosphamide (25\u00a0mg\/kg, intraperitoneal, once per week), ISD017 (10\u00a0mg\/kg, intraperitoneal, three times per week), or control vehicle for 8\u00a0weeks, and were analyzed for phenotypes. Both ISD017 and cyclophosphamide treatment increased long-term survival and reduced the severity of glomerulonephritis in <jats:italic>Fcgr2b<\/jats:italic>-deficient mice. While cyclophosphamide reduced activated B cells (B220<jats:sup>+<\/jats:sup>GL-7<jats:sup>+<\/jats:sup>), ISD017 decreased activated T cells (CD4<jats:sup>+<\/jats:sup>CD69<jats:sup>+<\/jats:sup>) and neutrophils (Ly6c<jats:sup>+<\/jats:sup>Ly6g<jats:sup>+<\/jats:sup>) in <jats:italic>Fcgr2b<\/jats:italic>-deficient mice. In addition, ISD017 reduced IL-1\u03b2 and interferon-inducible genes. In summary, ISD017 treatment in symptomatic 129.B6.<jats:italic>Fcgr2b<\/jats:italic>-deficient mice reduced the severity of glomerulonephritis and increased long-term survival. ISD017 worked comparably to cyclophosphamide for treating lupus nephritis in 129.B6.<jats:italic>Fcgr2b<\/jats:italic>-deficient mice. ISD017 reduced activated T cells and neutrophils, while cyclophosphamide targeted activated B cells. These results suggested that STING inhibitors can potentially be a new therapeutic drug for treating lupus.<\/jats:p>","DOI":"10.1038\/s41598-024-61597-z","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T12:02:02Z","timestamp":1715688122000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The STING inhibitor (ISD-017) reduces glomerulonephritis in 129.B6.Fcgr2b-deficient mice"],"prefix":"10.1038","volume":"14","author":[{"given":"Isara","family":"Alee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Papasara","family":"Chantawichitwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asada","family":"Leelahavanichkul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren R.","family":"Paludan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trairak","family":"Pisitkun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prapaporn","family":"Pisitkun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"issue":"8","key":"61597_CR1","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/nrrheum.2013.78","volume":"9","author":"JC Crispin","year":"2013","unstructured":"Crispin, J. C., Hedrich, C. M. & Tsokos, G. C. Gene-function studies in systemic lupus erythematosus. Nat. Rev. Rheumatol. 9(8), 476\u2013484 (2013).","journal-title":"Nat. Rev. Rheumatol."},{"key":"61597_CR2","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.coi.2020.10.014","volume":"67","author":"M Postal","year":"2020","unstructured":"Postal, M. et al. Type I interferon in the pathogenesis of systemic lupus erythematosus. Curr. Opin. Immunol. 67, 87\u201394 (2020).","journal-title":"Curr. Opin. Immunol."},{"issue":"3","key":"61597_CR3","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.immuni.2006.08.010","volume":"25","author":"J Banchereau","year":"2006","unstructured":"Banchereau, J. & Pascual, V. Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 25(3), 383\u2013392 (2006).","journal-title":"Immunity"},{"key":"61597_CR4","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.3389\/fimmu.2018.01088","volume":"9","author":"T Katsuyama","year":"2018","unstructured":"Katsuyama, T., Tsokos, G. C. & Moulton, V. R. Aberrant T cell signaling and subsets in systemic lupus erythematosus. Front. Immunol. 9, 1088 (2018).","journal-title":"Front. Immunol."},{"issue":"6","key":"61597_CR5","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/s41423-020-0445-4","volume":"17","author":"S Lee","year":"2020","unstructured":"Lee, S., Ko, Y. & Kim, T. J. Homeostasis and regulation of autoreactive B cells. Cell Mol. Immunol. 17(6), 561\u2013569 (2020).","journal-title":"Cell Mol. Immunol."},{"key":"61597_CR6","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.820927","volume":"13","author":"MI Barliana","year":"2022","unstructured":"Barliana, M. I., Afifah, N. N., Amalia, R., Hamijoyo, L. & Abdulah, R. Genetic polymorphisms and the clinical response to systemic lupus erythematosus treatment towards personalized medicine. Front. Pharmacol. 13, 820927 (2022).","journal-title":"Front. Pharmacol."},{"issue":"3","key":"61597_CR7","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1056\/NEJMoa1912196","volume":"382","author":"EF Morand","year":"2020","unstructured":"Morand, E. F. et al. Trial of anifrolumab in active systemic lupus erythematosus. N. Engl. J. Med. 382(3), 211\u2013221 (2020).","journal-title":"N. Engl. J. Med."},{"key":"61597_CR8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.980079","volume":"13","author":"KA Kirou","year":"2022","unstructured":"Kirou, K. A., Dall Era, M., Aranow, C. & Anders, H. J. Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment. Front. Immunol. 13, 980079 (2022).","journal-title":"Front. Immunol."},{"issue":"2","key":"61597_CR9","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/S1074-7613(00)00027-3","volume":"13","author":"S Bolland","year":"2000","unstructured":"Bolland, S. & Ravetch, J. V. Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis. Immunity 13(2), 277\u2013285 (2000).","journal-title":"Immunity"},{"issue":"5","key":"61597_CR10","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1002\/art.10257","volume":"46","author":"C Kyogoku","year":"2002","unstructured":"Kyogoku, C. et al. Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: Contribution of FCGR2B to genetic susceptibility. Arthritis Rheum. 46(5), 1242\u20131254 (2002).","journal-title":"Arthritis Rheum."},{"issue":"9","key":"61597_CR11","doi-asserted-by":"publisher","first-page":"101530","DOI":"10.1016\/j.isci.2020.101530","volume":"23","author":"A Thim-Uam","year":"2020","unstructured":"Thim-Uam, A. et al. STING mediates lupus via the activation of conventional dendritic cell maturation and plasmacytoid dendritic cell differentiation. iScience 23(9), 101530 (2020).","journal-title":"iScience"},{"issue":"6","key":"61597_CR12","first-page":"1362","volume":"101","author":"C Mohan","year":"1998","unstructured":"Mohan, C., Alas, E., Morel, L., Yang, P. & Wakeland, E. K. Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A\/H2B\/DNA subnucleosomes. J. Clin. Invest. 101(6), 1362\u201372 (1998).","journal-title":"J. Clin. Invest."},{"issue":"4","key":"61597_CR13","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1172\/JCI119217","volume":"99","author":"BP Tsao","year":"1997","unstructured":"Tsao, B. P. et al. Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus. J. Clin. Invest. 99(4), 725\u2013731 (1997).","journal-title":"J. Clin. Invest."},{"key":"61597_CR14","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12865-014-0047-y","volume":"15","author":"Y Kanari","year":"2014","unstructured":"Kanari, Y. et al. Dichotomy in FcgammaRIIB deficiency and autoimmune-prone SLAM haplotype clarifies the roles of the Fc receptor in development of autoantibodies and glomerulonephritis. BMC Immunol. 15, 47 (2014).","journal-title":"BMC Immunol."},{"key":"61597_CR15","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jaut.2015.06.011","volume":"63","author":"C Soni","year":"2015","unstructured":"Soni, C. et al. Distinct and synergistic roles of FcgammaRIIB deficiency and 129 strain-derived SLAM family proteins in the development of spontaneous germinal centers and autoimmunity. J. Autoimmun. 63, 31\u201346 (2015).","journal-title":"J. Autoimmun."},{"issue":"6045","key":"61597_CR16","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1126\/science.1206954","volume":"333","author":"F Li","year":"2011","unstructured":"Li, F. & Ravetch, J. V. Inhibitory Fcgamma receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science 333(6045), 1030\u20131034 (2011).","journal-title":"Science"},{"issue":"2","key":"61597_CR17","doi-asserted-by":"publisher","first-page":"775","DOI":"10.4049\/jimmunol.0901322","volume":"184","author":"TN Jorgensen","year":"2010","unstructured":"Jorgensen, T. N. et al. Development of murine lupus involves the combined genetic contribution of the SLAM and FcgammaR intervals within the Nba2 autoimmune susceptibility locus. J. Immunol. 184(2), 775\u2013786 (2010).","journal-title":"J. Immunol."},{"key":"61597_CR18","doi-asserted-by":"publisher","first-page":"31617","DOI":"10.1038\/srep31617","volume":"6","author":"XW Zhu","year":"2016","unstructured":"Zhu, X. W. et al. Comprehensive assessment of the association between FCGRs polymorphisms and the risk of systemic lupus erythematosus: Evidence from a meta-analysis. Sci. Rep. 6, 31617 (2016).","journal-title":"Sci. Rep."},{"issue":"5","key":"61597_CR19","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1093\/rheumatology\/kev433","volume":"55","author":"ASMW Tsang","year":"2016","unstructured":"Tsang, A. S. M. W. et al. Fc-gamma receptor polymorphisms differentially influence susceptibility to systemic lupus erythematosus and lupus nephritis. Rheumatology (Oxford). 55(5), 939\u2013948 (2016).","journal-title":"Rheumatology (Oxford)."},{"issue":"12","key":"61597_CR20","doi-asserted-by":"publisher","first-page":"2707","DOI":"10.1084\/jem.20160528","volume":"213","author":"L Xu","year":"2016","unstructured":"Xu, L. et al. Impairment on the lateral mobility induced by structural changes underlies the functional deficiency of the lupus-associated polymorphism FcgammaRIIB-T232. J. Exp. Med. 213(12), 2707\u20132727 (2016).","journal-title":"J. Exp. Med."},{"issue":"6","key":"61597_CR21","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.3899\/jrheum.150665","volume":"43","author":"K Kim","year":"2016","unstructured":"Kim, K. et al. Response to intravenous cyclophosphamide treatment for lupus nephritis associated with polymorphisms in the FCGR2B-FCRLA locus. J. Rheumatol. 43(6), 1045\u20131049 (2016).","journal-title":"J. Rheumatol."},{"issue":"9","key":"61597_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2022.103155","volume":"21","author":"Y Hu","year":"2022","unstructured":"Hu, Y. et al. Emerging role of the cGAS-STING signaling pathway in autoimmune diseases: Biologic function, mechanisms and clinical prospection. Autoimmun. Rev. 21(9), 103155 (2022).","journal-title":"Autoimmun. Rev."},{"issue":"6","key":"61597_CR23","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1056\/NEJMoa1312625","volume":"371","author":"Y Liu","year":"2014","unstructured":"Liu, Y. et al. Activated STING in a vascular and pulmonary syndrome. N. Engl. J. Med. 371(6), 507\u2013518 (2014).","journal-title":"N. Engl. J. Med."},{"issue":"3","key":"61597_CR24","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1084\/jem.20151464","volume":"213","author":"V Pokatayev","year":"2016","unstructured":"Pokatayev, V. et al. RNase H2 catalytic core Aicardi-Goutieres syndrome-related mutant invokes cGAS-STING innate immune-sensing pathway in mice. J. Exp. Med. 213(3), 329\u2013336 (2016).","journal-title":"J. Exp. Med."},{"issue":"15","key":"61597_CR25","doi-asserted-by":"publisher","first-page":"6719","DOI":"10.1128\/MCB.24.15.6719-6727.2004","volume":"24","author":"M Morita","year":"2004","unstructured":"Morita, M. et al. Gene-targeted mice lacking the Trex1 (DNase III) 3\u2019\u2013>5\u2019 DNA exonuclease develop inflammatory myocarditis. Mol. Cell Biol. 24(15), 6719\u20136727 (2004).","journal-title":"Mol. Cell Biol."},{"issue":"1","key":"61597_CR26","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.immuni.2011.11.018","volume":"36","author":"A Gall","year":"2012","unstructured":"Gall, A. et al. Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity 36(1), 120\u2013131 (2012).","journal-title":"Immunity"},{"issue":"4","key":"61597_CR27","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.4049\/jimmunol.0902592","volume":"184","author":"KM Nickerson","year":"2010","unstructured":"Nickerson, K. M. et al. TLR9 regulates TLR7- and MyD88-dependent autoantibody production and disease in a murine model of lupus. J. Immunol. 184(4), 1840\u20131848 (2010).","journal-title":"J. Immunol."},{"issue":"3","key":"61597_CR28","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.immuni.2006.07.013","volume":"25","author":"SR Christensen","year":"2006","unstructured":"Christensen, S. R. et al. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity 25(3), 417\u2013428 (2006).","journal-title":"Immunity"},{"issue":"7","key":"61597_CR29","doi-asserted-by":"publisher","first-page":"E710","DOI":"10.1073\/pnas.1420217112","volume":"112","author":"S Sharma","year":"2015","unstructured":"Sharma, S. et al. Suppression of systemic autoimmunity by the innate immune adaptor STING. Proc. Natl. Acad. Sci. USA 112(7), E710\u2013E717 (2015).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"3","key":"61597_CR30","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1084\/jem.20052438","volume":"203","author":"M Ehlers","year":"2006","unstructured":"Ehlers, M., Fukuyama, H., McGaha, T. L., Aderem, A. & Ravetch, J. V. TLR9\/MyD88 signaling is required for class switching to pathogenic IgG2a and 2b autoantibodies in SLE. J. Exp. Med. 203(3), 553\u2013561 (2006).","journal-title":"J. Exp. Med."},{"issue":"5780","key":"61597_CR31","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1126\/science.1124978","volume":"312","author":"P Pisitkun","year":"2006","unstructured":"Pisitkun, P. et al. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science 312(5780), 1669\u20131672 (2006).","journal-title":"Science"},{"issue":"26","key":"61597_CR32","doi-asserted-by":"publisher","first-page":"9970","DOI":"10.1073\/pnas.0603912103","volume":"103","author":"S Subramanian","year":"2006","unstructured":"Subramanian, S. et al. A Tlr7 translocation accelerates systemic autoimmunity in murine lupus. Proc. Natl. Acad. Sci. USA 103(26), 9970\u20139975 (2006).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"5","key":"61597_CR33","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.immuni.2007.09.009","volume":"27","author":"JA Deane","year":"2007","unstructured":"Deane, J. A. et al. Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation. Immunity. 27(5), 801\u2013810 (2007).","journal-title":"Immunity."},{"key":"61597_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103314","volume":"66","author":"T Prabakaran","year":"2021","unstructured":"Prabakaran, T. et al. A STING antagonist modulating the interaction with STIM1 blocks ER-to-Golgi trafficking and inhibits lupus pathology. EBioMedicine 66, 103314 (2021).","journal-title":"EBioMedicine"},{"issue":"6563","key":"61597_CR35","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/379346a0","volume":"379","author":"T Takai","year":"1996","unstructured":"Takai, T., Ono, M., Hikida, M., Ohmori, H. & Ravetch, J. V. Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice. Nature 379(6563), 346\u2013349 (1996).","journal-title":"Nature"},{"issue":"10","key":"61597_CR36","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14059","volume":"7","author":"VL Wolf","year":"2019","unstructured":"Wolf, V. L., Taylor, E. B. & Ryan, M. J. Cyclophosphamide treatment for hypertension and renal injury in an experimental model of systemic lupus erythematosus. Physiol. Rep. 7(10), e14059 (2019).","journal-title":"Physiol. Rep."},{"key":"61597_CR37","doi-asserted-by":"publisher","first-page":"10680","DOI":"10.1038\/ncomms10680","volume":"7","author":"CK Holm","year":"2016","unstructured":"Holm, C. K. et al. Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses. Nat. Commun. 7, 10680 (2016).","journal-title":"Nat. Commun."},{"key":"61597_CR38","doi-asserted-by":"publisher","first-page":"1010764","DOI":"10.3389\/fimmu.2022.1010764","volume":"13","author":"S Kumpunya","year":"2022","unstructured":"Kumpunya, S. et al. cGAS deficiency enhances inflammasome activation in macrophages and inflammatory pathology in pristane-induced lupus. Front. Immunol. 13, 1010764 (2022).","journal-title":"Front. Immunol."},{"key":"61597_CR39","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1111\/j.1749-6632.1997.tb52046.x","volume":"815","author":"O Chan","year":"1997","unstructured":"Chan, O., Madaio, M. P. & Shlomchik, M. J. The roles of B cells in MRL\/lpr murine lupus. Ann. N. Y. Acad. Sci. 815, 75\u201387 (1997).","journal-title":"Ann. N. Y. Acad. Sci."},{"issue":"6","key":"61597_CR40","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/j.immuni.2012.08.014","volume":"37","author":"P Pisitkun","year":"2012","unstructured":"Pisitkun, P. et al. Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis. Immunity 37(6), 1104\u20131115 (2012).","journal-title":"Immunity"},{"issue":"11","key":"61597_CR41","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1172\/JCI24179","volume":"115","author":"A Cappione 3rd","year":"2005","unstructured":"Cappione, A. 3rd. et al. Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus. J. Clin. Invest. 115(11), 3205\u20133216 (2005).","journal-title":"J. Clin. Invest."},{"key":"61597_CR42","first-page":"52533","volume":"98","author":"EC Steinbach","year":"2015","unstructured":"Steinbach, E. C., Gipson, G. R. & Sheikh, S. Z. Induction of murine intestinal inflammation by adoptive transfer of effector CD4+ CD45RB high T cells into immunodeficient mice. J. Vis. Exp. 98, 52533 (2015).","journal-title":"J. Vis. Exp."},{"key":"61597_CR43","doi-asserted-by":"publisher","first-page":"772","DOI":"10.3389\/fimmu.2019.00772","volume":"10","author":"AA Herrada","year":"2019","unstructured":"Herrada, A. A. et al. Innate immune cells\u2019 contribution to systemic lupus erythematosus. Front. Immunol. 10, 772 (2019).","journal-title":"Front. Immunol."},{"issue":"5","key":"61597_CR44","doi-asserted-by":"publisher","first-page":"2610","DOI":"10.1073\/pnas.0337679100","volume":"100","author":"EC Baechler","year":"2003","unstructured":"Baechler, E. C. et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc. Natl. Acad. Sci. USA 100(5), 2610\u20132615 (2003).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"6","key":"61597_CR45","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.immuni.2020.04.015","volume":"52","author":"C Soni","year":"2020","unstructured":"Soni, C. et al. Plasmacytoid dendritic cells and type I interferon promote extrafollicular B cell responses to extracellular self-DNA. Immunity 52(6), 1022\u20131038 (2020).","journal-title":"Immunity"},{"issue":"6121","key":"61597_CR46","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1126\/science.1232458","volume":"339","author":"L Sun","year":"2013","unstructured":"Sun, L., Wu, J., Du, F., Chen, X. & Chen, Z. J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339(6121), 786\u2013791 (2013).","journal-title":"Science"},{"issue":"47","key":"61597_CR47","doi-asserted-by":"publisher","first-page":"19386","DOI":"10.1073\/pnas.1215006109","volume":"109","author":"J Ahn","year":"2012","unstructured":"Ahn, J., Gutman, D., Saijo, S. & Barber, G. N. STING manifests self DNA-dependent inflammatory disease. Proc. Natl. Acad. Sci. USA 109(47), 19386\u201319391 (2012).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"42","key":"61597_CR48","doi-asserted-by":"publisher","first-page":"E5699","DOI":"10.1073\/pnas.1516465112","volume":"112","author":"D Gao","year":"2015","unstructured":"Gao, D. et al. Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases. Proc. Natl. Acad. Sci. USA 112(42), E5699\u2013E5705 (2015).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"10","key":"61597_CR49","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.autrev.2018.04.007","volume":"17","author":"C Ponticelli","year":"2018","unstructured":"Ponticelli, C., Escoli, R. & Moroni, G. Does cyclophosphamide still play a role in glomerular diseases?. Autoimmun. Rev. 17(10), 1022\u20131027 (2018).","journal-title":"Autoimmun. Rev."},{"issue":"3","key":"61597_CR50","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.kint.2016.05.017","volume":"90","author":"HJ Anders","year":"2016","unstructured":"Anders, H. J. & Rovin, B. A pathophysiology-based approach to the diagnosis and treatment of lupus nephritis. Kidney Int. 90(3), 493\u2013501 (2016).","journal-title":"Kidney Int."},{"issue":"8","key":"61597_CR51","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1093\/ndt\/gfv296","volume":"32","author":"A Malvar","year":"2017","unstructured":"Malvar, A. et al. Histologic versus clinical remission in proliferative lupus nephritis. Nephrol. Dial. Transplant. 32(8), 1338\u20131344 (2017).","journal-title":"Nephrol. Dial. Transplant."},{"issue":"1","key":"61597_CR52","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2014-000018","volume":"1","author":"A Zickert","year":"2014","unstructured":"Zickert, A., Sundelin, B., Svenungsson, E. & Gunnarsson, I. Role of early repeated renal biopsies in lupus nephritis. Lupus Sci. Med. 1(1), e000018 (2014).","journal-title":"Lupus Sci. Med."},{"key":"61597_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2022.100145","volume":"5","author":"LEC Andrade","year":"2022","unstructured":"Andrade, L. E. C., Damoiseaux, J., Vergani, D. & Fritzler, M. J. Anti-nuclear antibodies (ANA) as a criterion for classification and diagnosis of systemic autoimmune diseases. J. Transl. Autoimmun. 5, 100145 (2022).","journal-title":"J. Transl. Autoimmun."},{"key":"61597_CR54","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/978-1-4615-2427-4_12","volume":"347","author":"DM Klinman","year":"1994","unstructured":"Klinman, D. M., Shirai, A. & Ishigatsubo, Y. Polyclonal B cell activation and B cell cross-reactivity during autoantibody production in systemic lupus erythematosus. Adv. Exp. Med. Biol. 347, 115\u2013123 (1994).","journal-title":"Adv. Exp. Med. Biol."},{"key":"61597_CR55","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.3389\/fimmu.2019.01104","volume":"10","author":"OP Rekvig","year":"2019","unstructured":"Rekvig, O. P. The dsDNA, Anti-dsDNA antibody, and lupus nephritis: What we agree on, what must be done, and what the best strategy forward could be. Front. Immunol. 10, 1104 (2019).","journal-title":"Front. Immunol."},{"issue":"1","key":"61597_CR56","doi-asserted-by":"publisher","first-page":"2620","DOI":"10.1038\/s41598-018-20947-4","volume":"8","author":"C Thanadetsuntorn","year":"2018","unstructured":"Thanadetsuntorn, C. et al. The model of circulating immune complexes and interleukin-6 improves the prediction of disease activity in systemic lupus erythematosus. Sci. Rep. 8(1), 2620 (2018).","journal-title":"Sci. Rep."},{"issue":"8","key":"61597_CR57","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1016\/j.immuni.2021.07.015","volume":"54","author":"C Young","year":"2021","unstructured":"Young, C. & Brink, R. The unique biology of germinal center B cells. Immunity 54(8), 1652\u20131664 (2021).","journal-title":"Immunity"},{"issue":"1","key":"61597_CR58","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/j.1600-065X.2010.00912.x","volume":"236","author":"IJ Amanna","year":"2010","unstructured":"Amanna, I. J. & Slifka, M. K. Mechanisms that determine plasma cell lifespan and the duration of humoral immunity. Immunol. Rev. 236(1), 125\u2013138 (2010).","journal-title":"Immunol. Rev."},{"issue":"1","key":"61597_CR59","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s13075-015-0603-8","volume":"17","author":"T Fassbinder","year":"2015","unstructured":"Fassbinder, T. et al. Differential effects of cyclophosphamide and mycophenolate mofetil on cellular and serological parameters in patients with systemic lupus erythematosus. Arthritis Res. Ther. 17(1), 92 (2015).","journal-title":"Arthritis Res. Ther."},{"issue":"9","key":"61597_CR60","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1242\/dmm.016451","volume":"7","author":"SP Crampton","year":"2014","unstructured":"Crampton, S. P., Morawski, P. A. & Bolland, S. Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus. Dis. Models Mech. 7(9), 1033\u20131046 (2014).","journal-title":"Dis. Models Mech."},{"issue":"6","key":"61597_CR61","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1002\/eji.201646837","volume":"47","author":"D Cibrian","year":"2017","unstructured":"Cibrian, D. & Sanchez-Madrid, F. CD69: From activation marker to metabolic gatekeeper. Eur. J. Immunol. 47(6), 946\u2013953 (2017).","journal-title":"Eur. J. Immunol."},{"issue":"6","key":"61597_CR62","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/nrrheum.2010.64","volume":"6","author":"L R\u00f6nnblom","year":"2010","unstructured":"R\u00f6nnblom, L. & Elkon, K. B. Cytokines as therapeutic targets in SLE. Nat. Rev. Rheumatol. 6(6), 339\u2013347 (2010).","journal-title":"Nat. Rev. Rheumatol."},{"issue":"5","key":"61597_CR63","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1177\/096120339700600507","volume":"6","author":"CC Su","year":"1997","unstructured":"Su, C. C., Shau, W. Y., Wang, C. R., Chuang, C. Y. & Chen, C. Y. CD69 to CD3 ratio of peripheral blood mononuclear cells as a marker to monitor systemic lupus erythematosus disease activity. Lupus 6(5), 449\u2013454 (1997).","journal-title":"Lupus"},{"issue":"5","key":"61597_CR64","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1097\/BOR.0000000000000197","volume":"27","author":"CK Smith","year":"2015","unstructured":"Smith, C. K. & Kaplan, M. J. The role of neutrophils in the pathogenesis of systemic lupus erythematosus. Curr. Opin. Rheumatol. 27(5), 448\u2013453 (2015).","journal-title":"Curr. Opin. Rheumatol."},{"key":"61597_CR65","doi-asserted-by":"publisher","first-page":"139","DOI":"10.4172\/2155-9899.1000139","volume":"4","author":"Y Yu","year":"2013","unstructured":"Yu, Y. & Su, K. Neutrophil extracellular traps and systemic lupus erythematosus. J. Clin. Cell. Immunol. 4, 139 (2013).","journal-title":"J. Clin. Cell. Immunol."},{"issue":"1","key":"61597_CR66","doi-asserted-by":"publisher","first-page":"118","DOI":"10.4049\/jimmunol.141.1.118","volume":"141","author":"JM Boswell","year":"1988","unstructured":"Boswell, J. M., Yui, M. A., Endres, S., Burt, D. W. & Kelley, V. E. Novel and enhanced IL-1 gene expression in autoimmune mice with lupus. J. Immunol. 141(1), 118\u201324 (1988).","journal-title":"J. Immunol."},{"issue":"1","key":"61597_CR67","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/ki.1996.290","volume":"50","author":"S Lemay","year":"1996","unstructured":"Lemay, S., Mao, C. & Singh, A. K. Cytokine gene expression in the MRL\/lpr model of lupus nephritis. Kidney Int. 50(1), 85\u201393 (1996).","journal-title":"Kidney Int."},{"key":"61597_CR68","doi-asserted-by":"publisher","first-page":"1162799","DOI":"10.3389\/fimmu.2023.1162799","volume":"14","author":"SN Loftus","year":"2023","unstructured":"Loftus, S. N. et al. Loss of interleukin-1 beta is not protective in the lupus-prone NZM2328 mouse model. Front. Immunol. 14, 1162799 (2023).","journal-title":"Front. Immunol."},{"issue":"5","key":"61597_CR69","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.cell.2017.09.039","volume":"171","author":"MM Gaidt","year":"2017","unstructured":"Gaidt, M. M. et al. The DNA inflammasome in human myeloid cells is initiated by a STING-cell death program upstream of NLRP3. Cell 171(5), 1110\u20131124 (2017).","journal-title":"Cell"},{"issue":"11","key":"61597_CR70","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41576-019-0151-1","volume":"20","author":"M Motwani","year":"2019","unstructured":"Motwani, M., Pesiridis, S. & Fitzgerald, K. A. DNA sensing by the cGAS-STING pathway in health and disease. Nat. Rev. Genet. 20(11), 657\u2013674 (2019).","journal-title":"Nat. Rev. Genet."},{"key":"61597_CR71","doi-asserted-by":"publisher","first-page":"137","DOI":"10.3389\/fimmu.2016.00137","volume":"7","author":"J Yuen","year":"2016","unstructured":"Yuen, J. et al. NETosing neutrophils activate complement both on their own NETs and bacteria via alternative and non-alternative pathways. Front. Immunol. 7, 137 (2016).","journal-title":"Front. Immunol."},{"issue":"20","key":"61597_CR72","doi-asserted-by":"publisher","first-page":"11421","DOI":"10.1093\/nar\/gkaa873","volume":"48","author":"L Dalskov","year":"2020","unstructured":"Dalskov, L. et al. Characterization of distinct molecular interactions responsible for IRF3 and IRF7 phosphorylation and subsequent dimerization. Nucleic Acids Res. 48(20), 11421\u201311433 (2020).","journal-title":"Nucleic Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-61597-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-61597-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-61597-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T12:15:58Z","timestamp":1715688958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-61597-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,14]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["61597"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-61597-z","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,14]]},"assertion":[{"value":"17 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"SRP owns shares in ISD Immunotech, which owns the patent for ISD017 (WO2014166502A2). The patent was issued by CKH. None of the other authors have conflicts to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11020"}}