{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T20:24:19Z","timestamp":1788121459552,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81830049"],"award-info":[{"award-number":["81830049"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81761128012"],"award-info":[{"award-number":["81761128012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic lupus erythematosus (SLE) involves kidney damage, and the inflammasome\u2010caspase\u20101 axis has been demonstrated to promote renal pathogenesis. The present study was designed to explore the function of the Absent in Melanoma 2 (Aim2) protein in SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female wild\u2010type <jats:italic>Aim2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>, <jats:italic>Aim2<jats:sup>\u2212\/\u2212<\/jats:sup>Ifnar1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>, <jats:italic>Aim2<jats:sup>\u2212\/\u2212<\/jats:sup>Rag1<jats:sup>\u2212\/\u2212<\/jats:sup>,<\/jats:italic> and <jats:italic>Asc<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice ages 8\u201310 weeks received 1 intraperitoneal injection of 500 \u03bcl pristane or saline, and survival of mice was monitored twice a week for 6 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The absence of <jats:italic>Aim2<\/jats:italic>, but not <jats:italic>Asc<\/jats:italic>, led to enhanced SLE in mice that received pristane treatment. Increased immune cell infiltration and type I interferon (IFN) signatures in the kidneys of <jats:italic>Aim2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice coincided with severity of lupus, which was alleviated by blockade of <jats:italic>Ifnar1<\/jats:italic>\u2010mediated signal. Adaptive immune cells were also involved in the glomerular lesions of <jats:italic>Aim2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice after pristane challenge. Importantly, even in the absence of pristane, plasmacytoid dendritic cells in the kidneys of <jats:italic>Aim2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice were significantly increased compared to control animals. Accordingly, transcriptome analysis revealed that <jats:italic>Aim2<\/jats:italic> deficiency led to enhanced expression of type I IFN\u2013induced genes in the kidneys even at an early developmental stage. Mechanistically, Aim2 bound ubiquitin\u2010conjugating enzyme 2i (Ube2i), which mediates sumoylation\u2010based suppression of type I IFN expression deficiency of <jats:italic>Aim2<\/jats:italic> decreased cellular sumoylation, resulting in an augmented type I IFN signature and kidney pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present study demonstrates a critical role for Aim2 in an optimal <jats:italic>Ube2i<\/jats:italic>\u2010mediated sumoylation\u2010based suppression of type I IFN generation and development of SLE. As such, the <jats:italic>Aim2<\/jats:italic>\u2013<jats:italic>Ube2i<\/jats:italic> axis can thus be a novel target for intervention in SLE.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41677","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T10:03:55Z","timestamp":1612865035000},"page":"1467-1477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["<i>Aim2<\/i> Couples With <i>Ube2i<\/i> for Sumoylation\u2010Mediated Repression of Interferon Signatures in Systemic Lupus\u00a0Erythematosus"],"prefix":"10.1002","volume":"73","author":[{"given":"Ailing","family":"Lu","sequence":"first","affiliation":[{"name":"Center for Microbes Development and Health Key Laboratory of Molecular Virology and Immunology Institut Pasteur of Shanghai University of Chinese Academy of Sciences Shanghai, China, and Center for Autoimmune Musculoskeletal and Hemaopoietic Diseases, Feinstein Institutes for 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