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Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115

Cellular & Molecular Immunology volume 21, pages 275–291 (2024)Cite this article

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Abstract

STING (also known as MITA) is an adaptor protein that mediates cytoplasmic DNA-triggered signaling, and aberrant activation of STING/MITA by cytosolic self-DNA or gain-of-function mutations causes severe inflammation. Here, we show that STING-mediated inflammation and autoimmunity are promoted by RNF115 and alleviated by the RNF115 inhibitor disulfiram (DSF). Knockout of RNF115 or treatment with DSF significantly inhibit systemic inflammation and autoimmune lethality and restore immune cell development in Trex1–/– mice and STINGN153S/WT bone marrow chimeric mice. In addition, knockdown or pharmacological inhibition of RNF115 substantially downregulate the expression of IFN-α, IFN-γ and proinflammatory cytokines in PBMCs from patients with systemic lupus erythematosus (SLE) who exhibit high concentrations of dsDNA in peripheral blood. Mechanistically, knockout or inhibition of RNF115 impair the oligomerization and Golgi localization of STING in various types of cells transfected with cGAMP and in organs and cells from Trex1–/– mice. Interestingly, knockout of RNF115 inhibits the activation and Golgi localization of STINGN153S as well as the expression of proinflammatory cytokines in myeloid cells but not in endothelial cells or fibroblasts. Taken together, these findings highlight the RNF115-mediated cell type-specific regulation of STING and STINGN153S and provide potential targeted intervention strategies for STING-related autoimmune diseases.

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Data availability

All the other data supporting the findings of this study within the article and its Supplementary Information files are available from the corresponding author upon reasonable request. A reporting summary for this article is available as a Supplementary Information file.

References

  1. Tan X, Sun L, Chen J, Chen ZJ. Detection of microbial infections through innate immune sensing of nucleic acids. Annu Rev Microbiol. 2018;72:447–78.

    Article  PubMed  CAS  Google Scholar 

  2. Zhong B, Shu HB. MITA/STING-mediated antiviral immunity and autoimmunity: the evolution, mechanism, and intervention. Curr Opin Immunol. 2022;78:102248.

    Article  PubMed  CAS  Google Scholar 

  3. Zhang ZD, Zhong B. Regulation and function of the cGAS-MITA/STING axis in health and disease. Cell Insight. 2022;1:100001.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Li XD, Wu J, Gao D, Wang H, Sun L, Chen ZJ. Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects. Science. 2013;341:1390–4.

    Article  ADS  PubMed  CAS  Google Scholar 

  5. 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;339:786–91.

    Article  ADS  PubMed  CAS  Google Scholar 

  6. Wu J, Sun L, Chen X, Du F, Shi H, Chen C, et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013;339:826–30.

    Article  ADS  PubMed  CAS  Google Scholar 

  7. Sun W, Li Y, Chen L, Chen H, You F, Zhou X, et al. ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization. Proc Natl Acad Sci USA. 2009;106:8653–8.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  8. Zhong B, Yang Y, Li S, Wang YY, Li Y, Diao F, et al. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity. 2008;29:538–50.

    Article  PubMed  CAS  Google Scholar 

  9. Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature. 2008;455:674–8.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  10. Fang R, Jiang Q, Guan Y, Gao P, Zhang R, Zhao Z, et al. Golgi apparatus-synthesized sulfated glycosaminoglycans mediate polymerization and activation of the cGAMP sensor STING. Immunity. 2021;54:962–975.e968.

    Article  PubMed  CAS  Google Scholar 

  11. Hopfner KP, Hornung V. Molecular mechanisms and cellular functions of cGAS-STING signalling. Nat Rev Mol Cell Biol. 2020;21:501–21.

    Article  PubMed  CAS  Google Scholar 

  12. Zierhut C, Funabiki H. Regulation and consequences of cGAS activation by Self-DNA. Trends Cell Biol. 2020;30:594–605.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Ahn J, Gutman D, Saijo S, Barber GN. STING manifests self DNA-dependent inflammatory disease. Proc Natl Acad Sci USA. 2012;109:19386–91.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  14. 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;6:49–56.

    Article  PubMed  CAS  Google Scholar 

  15. Decout A, Katz JD, Venkatraman S, Ablasser A. The cGAS-STING pathway as a therapeutic target in inflammatory diseases. Nat Rev Immunol. 2021;21:548–69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Crow YJ, Hayward BE, Parmar R, Robins P, Leitch A, Ali M, et al. Mutations in the gene encoding the 3’-5’ DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus. Nat Genet. 2006;38:917–20.

    Article  PubMed  CAS  Google Scholar 

  17. Sakai T, Miyazaki T, Shin DM, Kim YS, Qi CF, Fariss R, et al. DNase-active TREX1 frame-shift mutants induce serologic autoimmunity in mice. J Autoimmun. 2017;81:13–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Grieves JL, Fye JM, Harvey S, Grayson JM, Hollis T, Perrino FW. Exonuclease TREX1 degrades double-stranded DNA to prevent spontaneous lupus-like inflammatory disease. Proc Natl Acad Sci USA. 2015;112:5117–22.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  19. Stetson DB, Ko JS, Heidmann T, Medzhitov R. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell. 2008;134:587–98.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Gao KM, Marshak-Rothstein A, Fitzgerald KA. Type-1 interferon-dependent and -independent mechanisms in cyclic GMP-AMP synthase-stimulator of interferon genes-driven auto-inflammation. Curr Opin Immunol. 2023;80:102280.

    Article  PubMed  CAS  Google Scholar 

  21. Giordano AMS, Luciani M, Gatto F, Abou Alezz M, Beghe C, Della Volpe L, et al. DNA damage contributes to neurotoxic inflammation in Aicardi-Goutieres syndrome astrocytes. J Exp Med. 2022;219:e20211121.

  22. Ahn J, Ruiz P, Barber GN. Intrinsic self-DNA triggers inflammatory disease dependent on STING. J Immunol. 2014;193:4634–42.

    Article  PubMed  CAS  Google Scholar 

  23. Fremond ML, Hadchouel A, Berteloot L, Melki I, Bresson V, Barnabei L, et al. Overview of STING-associated vasculopathy with onset in infancy (SAVI) among 21 patients. J Allergy Clin Immunol Pr. 2021;9:803–818.e811.

    Article  CAS  Google Scholar 

  24. Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Sanchez GAM, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014;371:507–18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Siedel H, Roers A, Rosen-Wolff A, Luksch H. Type I interferon-independent T cell impairment in a Tmem173 N153S/WT mouse model of STING associated vasculopathy with onset in infancy (SAVI). Clin Immunol. 2020;216:108466.

    Article  PubMed  CAS  Google Scholar 

  26. Motwani M, Pawaria S, Bernier J, Moses S, Henry K, Fang T, et al. Hierarchy of clinical manifestations in SAVI N153S and V154M mouse models. Proc Natl Acad Sci USA. 2019;116:7941–50.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  27. Wu J, Chen YJ, Dobbs N, Sakai T, Liou J, Miner JJ, et al. STING-mediated disruption of calcium homeostasis chronically activates ER stress and primes T cell death. J Exp Med. 2019;216:867–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Warner JD, Irizarry-Caro RA, Bennion BG, Ai TL, Smith AM, Miner CA, et al. STING-associated vasculopathy develops independently of IRF3 in mice. J Exp Med. 2017;214:3279–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Luksch H, Stinson WA, Platt DJ, Qian W, Kalugotla G, Miner CA, et al. STING-associated lung disease in mice relies on T cells but not type I interferon. J Allergy Clin Immunol. 2019;144:254–266.e258.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. 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;18:157–68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Aringer M, Costenbader K, Dorner T, Johnson SR. Advances in SLE classification criteria. J Autoimmun. 2022;132:102845.

    Article  PubMed  Google Scholar 

  32. Barrat FJ, Crow MK, Ivashkiv LB. Interferon target-gene expression and epigenomic signatures in health and disease. Nat Immunol. 2019;20:1574–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Soni C, Perez OA, Voss WN, Pucella JN, Serpas L, Mehl J, et al. Plasmacytoid dendritic cells and type I interferon promote extrafollicular B cell responses to extracellular self-DNA. Immunity. 2020;52:1022–1038.e1027.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Hagberg N, Berggren O, Leonard D, Weber G, Bryceson YT, Alm GV, et al. IFN-alpha production by plasmacytoid dendritic cells stimulated with RNA-containing immune complexes is promoted by NK cells via MIP-1beta and LFA-1. J Immunol. 2011;186:5085–94.

    Article  PubMed  CAS  Google Scholar 

  35. Namjou B, Kothari PH, Kelly JA, Glenn SB, Ojwang JO, Adler A, et al. Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort. Genes Immun. 2011;12:270–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee YA, et al. Mutations in the gene encoding the 3’-5’ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet. 2007;39:1065–7.

    Article  PubMed  CAS  Google Scholar 

  37. An J, Durcan L, Karr RM, Briggs TA, Rice GI, Teal TH, et al. Expression of cyclic GMP-AMP synthase in patients with systemic lupus erythematosus. Arthritis Rheumatol. 2017;69:800–7.

    Article  PubMed  CAS  Google Scholar 

  38. Caielli S, Cardenas J, de Jesus AA, Baisch J, Walters L, Blanck JP, et al. Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE. Cell. 2021;184:4464–4479.e4419.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Kato Y, Park J, Takamatsu H, Konaka H, Aoki W, Aburaya S, et al. Apoptosis-derived membrane vesicles drive the cGAS-STING pathway and enhance type I IFN production in systemic lupus erythematosus. Ann Rheum Dis. 2018;77:1507–15.

    Article  PubMed  CAS  Google Scholar 

  40. Michailidou K, Beesley J, Lindstrom S, Canisius S, Dennis J, Lush MJ, et al. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer. Nat Genet. 2015;47:373–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Wang MX, Liuyu T, Zhang ZD. Multifaceted roles of the E3 ubiquitin ligase RING finger protein 115 in immunity and diseases. Front Immunol. 2022;13:936579.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Zhang ZD, Li HX, Gan H, Tang Z, Guo YY, Yao SQ, et al. RNF115 inhibits the Post-ER trafficking of TLRs and TLRs-mediated immune responses by catalyzing K11-linked ubiquitination of RAB1A and RAB13. Adv Sci (Weinh). 2022;9:e2105391.

    Article  PubMed  Google Scholar 

  43. Zhang ZD, Xiong TC, Yao SQ, Wei MC, Chen M, Lin D, et al. RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA. Nat Commun. 2020;11:5536.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  44. Hasan M, Gonugunta VK, Dobbs N, Ali A, Palchik G, Calvaruso MA, et al. Chronic innate immune activation of TBK1 suppresses mTORC1 activity and dysregulates cellular metabolism. Proc Natl Acad Sci USA. 2017;114:746–51.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  45. Zhang Q, Tang Z, An R, Ye L, Zhong B. USP29 maintains the stability of cGAS and promotes cellular antiviral responses and autoimmunity. Cell Res. 2020;30:914–27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Crow YJ, Jackson AP, Roberts E, van Beusekom E, Barth P, Corry P, et al. Aicardi-Goutieres syndrome displays genetic heterogeneity with one locus (AGS1) on chromosome 3p21. Am J Hum Genet. 2000;67:213–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Ahn J, Son S, Oliveira SC, Barber GN. STING-dependent signaling underlies IL-10 controlled inflammatory colitis. Cell Rep. 2017;21:3873–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Brahemi G, Kona FR, Fiasella A, Buac D, Soukupova J, Brancale A, et al. Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast cancer. J Med Chem. 2010;53:2757–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Hung T, Pratt GA, Sundararaman B, Townsend MJ, Chaivorapol C, Bhangale T, et al. The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression. Science. 2015;350:455–9.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  50. Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, et al. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011;472:481–5.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  51. Saldanha RG, Balka KR, Davidson S, Wainstein BK, Wong M, Macintosh R, et al. A mutation outside the dimerization domain causing atypical STING-associated vasculopathy with onset in infancy. Front Immunol. 2018;9:1535.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Konno H, Chinn IK, Hong D, Orange JS, Lupski JR, Mendoza A, et al. Pro-inflammation associated with a gain-of-function mutation (R284S) in the innate immune sensor STING. Cell Rep. 2018;23:1112–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Kawazoe N, Eto T, Abe I, Takishita S, Ueno M, Kobayashi K, et al. Pathophysiology in malignant hypertension: with special reference to the renin-angiotensin system. Clin Cardiol. 1987;10:513–8.

    Article  PubMed  CAS  Google Scholar 

  54. Morgan WK. On dust, disability, and death. Am Rev Respir Dis. 1986;134:639–41.

    PubMed  CAS  Google Scholar 

  55. Kumaran Satyanarayanan S, El Kebir D, Soboh S, Butenko S, Sekheri M, Saadi J, et al. IFN-beta is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation. Nat Commun. 2019;10:3471.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  56. Perkins DJ, Rajaiah R, Tennant SM, Ramachandran G, Higginson EE, Dyson TN, et al. Salmonella typhimurium co-opts the host type I IFN system to restrict macrophage innate immune transcriptional responses selectively. J Immunol. 2015;195:2461–71.

    Article  PubMed  CAS  Google Scholar 

  57. Doghri Y, Dubreil L, Lalanne V, Helissen O, Fleurisson R, Thorin C, et al. Soluble guanylate cyclase chronic stimulation effects on cardiovascular reactivity in cafeteria diet-induced rat model of metabolic syndrome. Eur J Pharm. 2021;899:173978.

    Article  CAS  Google Scholar 

  58. Gui X, Yang H, Li T, Tan X, Shi P, Li M, et al. Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature. 2019;567:262–6.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  59. Liu D, Wu H, Wang C, Li Y, Tian H, Siraj S, et al. STING directly activates autophagy to tune the innate immune response. Cell Death Differ. 2019;26:1735–49.

    Article  PubMed  CAS  Google Scholar 

  60. Bilkei-Gorzo O, Heunis T, Marin-Rubio JL, Cianfanelli FR, Raymond BBA, Inns J, et al. The E3 ubiquitin ligase RNF115 regulates phagosome maturation and host response to bacterial infection. EMBO J. 2022;41:e108970.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Li R, Gu Z, Zhang X, Yu J, Feng J, Lou Y, et al. RNF115 deletion inhibits autophagosome maturation and growth of gastric cancer. Cell Death Dis. 2020;11:810.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Nityanandam R, Serra-Moreno R. BCA2/Rabring7 targets HIV-1 Gag for lysosomal degradation in a tetherin-independent manner. PLoS Pathog. 2014;10:e1004151.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Chen C, Xu P. Cellular functions of cGAS-STING signaling. Trends Cell Biol. 2022.

  64. Zhang D, Liu Y, Zhu Y, Zhang Q, Guan H, Liu S, et al. A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis. Nat Cell Biol. 2022;24:766–82.

    Article  PubMed  CAS  Google Scholar 

  65. Mukai K, Ogawa E, Uematsu R, Kuchitsu Y, Kiku F, Uemura T, et al. Homeostatic regulation of STING by retrograde membrane traffic to the ER. Nat Commun. 2021;12:61.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  66. Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, et al. TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS/STING in ALS. Cell. 2020;183:636–649.e618.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. McCauley ME, O’Rourke JG, Yanez A, Markman JL, Ho R, Wang X, et al. C9orf72 in myeloid cells suppresses STING-induced inflammation. Nature. 2020;585:96–101.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  68. Lepelley A, Martin-Niclos MJ, Le Bihan M, Marsh JA, Uggenti C, Rice GI, et al. Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling, J Exp Med. 2020;217:e20200600.

  69. Deng Z, Chong Z, Law CS, Mukai K, Ho FO, Martinu T, et al. A defect in COPI-mediated transport of STING causes immune dysregulation in COPA syndrome, J Exp Med. 2020;217:e20201045.

  70. Sliter DA, Martinez J, Hao L, Chen X, Sun N, Fischer TD, et al. Parkin and PINK1 mitigate STING-induced inflammation. Nature. 2018;561:258–62.

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  71. Xiong TC, Wei MC, Li FX, Shi M, Gan H, Tang Z, et al. The E3 ubiquitin ligase ARIH1 promotes antiviral immunity and autoimmunity by inducing mono-ISGylation and oligomerization of cGAS. Nat Commun. 2022;13:5973.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  72. Wang J, Li Y, Wang P, Han G, Zhang T, Chang J, et al. Leukemogenic chromatin alterations promote AML leukemia stem cells via a KDM4C-ALKBH5-AXL signaling axis. Cell Stem Cell. 2020;27:81–97.e88.

    Article  PubMed  Google Scholar 

  73. Yu K, Guo YY, Liuyu T, Wang P, Zhang ZD, Lin D, et al. The deubiquitinase OTUD4 inhibits the expression of antimicrobial peptides in Paneth cells to support intestinal inflammation and bacterial infection. Cell Insight. 2023;2:100100.

    Article  PubMed  PubMed Central  Google Scholar 

  74. An R, Wang P, Guo H, Liuyu T, Zhong B, Zhang ZD. USP2 promotes experimental colitis and bacterial infections by inhibiting the proliferation of myeloid cells and remodeling the extracellular matrix network. Cell Insight. 2022;1:100047.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Guo YY, Gao Y, Hu YR, Zhao Y, Jiang D, Wang Y, et al. The transient receptor potential vanilloid 2 (TRPV2) channel facilitates virus infection through the Ca(2+) -LRMDA axis in myeloid cells. Adv Sci (Weinh). 2022;9:e2202857.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Dr. Haojian Zhang (Wuhan University) for the reagents and the members of the Zhong laboratory and the core facilities of the Medical Research Institute for their technical help. This study was supported by grants from the National Key Research and Development Program of China (Grant Nos. 2022YFC3401500 and 2023YFC2306100), the Natural Science Foundation of China (Grant Nos. 31930040, 32070900, 82000670, 32270951, 32200710, and 823B1006), the Fundamental Research Funds for the Central Universities (Grant Nos. 2042022kf1187, 2042022kf1123 and 2042022dx0003), the Major Scientific and Technological Project of Hubei Province (Grant No. 2022ACA005), the Translational Medicine and Interdisciplinary Research Joint Found of Zhongnan Hospital of Wuhan University (Grant. No. ZNJC202218), and the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (Grant No. 2020PT320-004).

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China

    Zhi-Dong Zhang, Chang-Rui Shi, Fang-Xu Li, Hu Gan, Xin Shuai, Yu-Lin Lin, Tian-Chen Xiong & Bo Zhong

  2. Department of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China

    Zhi-Dong Zhang, Chang-Rui Shi, Hu Gan, Xin Shuai, Yu-Lin Lin & Bo Zhong

  3. TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China

    Zhi-Dong Zhang & Bo Zhong

  4. Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, 430071, China

    Zhi-Dong Zhang & Bo Zhong

  5. Department of Rheumatology and Immunology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China

    Yanhong Wei, Qianhui Zhang, Min Chen & Xiaoqi Chen

  6. Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Dandan Lin

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Contributions

BZ, DL, and XC designed and supervised the study; ZDZ performed the experiments; CRS, FXL, XSYLL and TCX helped with the mouse experiments; HG performed mass spectrometry analysis. YHW, QHZ, MC, and XC collected peripheral blood from the healthy donors and SLE patients; BZ, DL, and ZDZ wrote the paper. All the authors analyzed the data.

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Correspondence to Xiaoqi Chen, Bo Zhong or Dandan Lin.

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Zhang, ZD., Shi, CR., Li, FX. et al. Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115. Cell Mol Immunol 21, 275–291 (2024). https://doi.org/10.1038/s41423-024-01131-3

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