{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:28:02Z","timestamp":1740126482701,"version":"3.37.3"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T00:00:00Z","timestamp":1532304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31670898","81273300","31470880","31370894","31170878","31770962"],"award-info":[{"award-number":["31670898","81273300","31470880","31370894","31170878","31770962"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,21]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>B6\/lpr mouse strain is a well-known systemic lupus erythematosus murine model characterized by uncontrolled lymphoproliferation and autoantibody production. However, it displays a delayed and mild development of lupus nephritis (LN), which is not conducive to the research of the pathogenesis and therapeutic strategies of this condition. Our previous study demonstrated that activated lymphocyte-derived DNA (ALD-DNA) could induce high urine protein levels and severe glomerulonephritis (GN) in BALB\/c mice. In the present study, we tried to remedy delayed urine protein production and mild GN in B6\/lpr mice via ALD-DNA immunization. We found that urine protein levels were enhanced significantly in B6\/lpr mice 4\u00a0weeks after ALD-DNA immunization compared with those in unactivated lymphocyte-derived (UnALD)-DNA- and phosphate-buffered saline (PBS)-treated controls. Moreover, more serious GN and glomerular immune complex were observed in ALD-DNA-immunized B6\/lpr mice. We further explored the mechanism, and found that ALD-DNA immunization promoted T helper type 17 (Th17) cell enrichment remarkably, which enhanced the proportion of autoantibody-secreting plasma cells and promoted the production of anti-dsDNA autoantibodies, leading to accelerated and aggravated LN. Our data demonstrated that ALD-DNA immunization could remedy delayed urine protein production and mild GN in B6\/lpr mouse, which makes it more suitable for studies on the pathogenesis of and therapeutic strategies against LN.<\/jats:p>","DOI":"10.1111\/cei.13147","type":"journal-article","created":{"date-parts":[[2018,4,28]],"date-time":"2018-04-28T16:04:01Z","timestamp":1524931441000},"page":"302-312","source":"Crossref","is-referenced-by-count":1,"title":["Administration of activated lymphocyte-derived DNA accelerates and aggravates lupus nephritis in B6\/lpr mice: a new approach to modify a lupus murine model"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5678-0224","authenticated-orcid":false,"given":"Y","family":"Zhu","sequence":"first","affiliation":[{"name":"Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Yue","sequence":"additional","affiliation":[{"name":"Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,7,23]]},"reference":[{"key":"2021120808392188700_cei13147-bib-0001","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0049-0172(95)80004-2","article-title":"Autoantibodies in the diagnosis of systemic rheumatic diseases","volume":"24","author":"von M\u00fchlen","year":"1995","journal-title":"Semin Arthritis Rheum"},{"key":"2021120808392188700_cei13147-bib-0002","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/978-0-387-68566-3_15","volume-title":"Primer on the rheumatic diseases","author":"Buyon","year":"2008"},{"key":"2021120808392188700_cei13147-bib-0003","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1056\/NEJM200108023450506","article-title":"Autoimmune diseases","volume":"345","author":"Davidson","year":"2001","journal-title":"N Engl J Med"},{"key":"2021120808392188700_cei13147-bib-0004","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1097\/00002281-200109000-00002","article-title":"Mortality and causes of death in systemic lupus erythematosus","volume":"13","author":"Trager","year":"2001","journal-title":"Curr Opin Rheumatol"},{"key":"2021120808392188700_cei13147-bib-0005","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1002\/art.1780340803","article-title":"Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only","volume":"34","author":"Steinberg","year":"1991","journal-title":"Arthritis Rheum"},{"key":"2021120808392188700_cei13147-bib-0006","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/rheumatology\/39.1.18","article-title":"Systemic lupus erythematosus \u2013 messages from experimental models","volume":"39","author":"Stoll","year":"2000","journal-title":"Rheumatology (Oxf)"},{"key":"2021120808392188700_cei13147-bib-0007","doi-asserted-by":"crossref","first-page":"271694","DOI":"10.1155\/2011\/271694","article-title":"Murine models of systemic lupus erythematosus","volume":"2011","author":"Perry","year":"2011","journal-title":"J Biomed Biotechnol"},{"key":"2021120808392188700_cei13147-bib-0008","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1084\/jem.154.5.1671","article-title":"Deficient interleukin 2 activity in MRL\/Mp and C57BL\/6J mice bearing the lpr gene","volume":"154","author":"Wofsy","year":"1981","journal-title":"J Exp Med"},{"key":"2021120808392188700_cei13147-bib-0009","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1146\/annurev.iy.09.040191.001331","article-title":"Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease","volume":"9","author":"Cohen","year":"1991","journal-title":"Annu Rev Immunol"},{"key":"2021120808392188700_cei13147-bib-0010","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0167-5699(95)80069-7","article-title":"Fas and Fas ligand: lpr and gld mutations","volume":"16","author":"Nagata","year":"1995","journal-title":"Immunol Today"},{"key":"2021120808392188700_cei13147-bib-0011","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.1016\/S0091-6749(97)70013-7","article-title":"Why do defects in the Fas\u2013Fas ligand system cause autoimmunity?","volume":"100","author":"Suda","year":"1997","journal-title":"J Allergy Clin Immunol"},{"key":"2021120808392188700_cei13147-bib-0012","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1006\/cimm.1998.1290","article-title":"Immunological and pathological consequences of mutations in both Fas and Fas ligand","volume":"186","author":"Weintraub","year":"1998","journal-title":"Cell Immunol"},{"key":"2021120808392188700_cei13147-bib-0013","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.4049\/jimmunol.165.2.1036","article-title":"Fas and Fas ligand mutations inhibit autoantibody production in pristane-induced lupus","volume":"165","author":"Satoh","year":"2000","journal-title":"J Immunol"},{"key":"2021120808392188700_cei13147-bib-0014","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/eji.200323794","article-title":"FcgammaRIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune disease","volume":"33","author":"Yajima","year":"2003","journal-title":"Eur J Immunol"},{"key":"2021120808392188700_cei13147-bib-0015","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1093\/intimm\/dxm017","article-title":"PI3K\/AKT\/mTOR hypersignaling in autoimmune lymphoproliferative disease engendered by the epistatic interplay of Sle1b and FASlpr","volume":"19","author":"Xie","year":"2007","journal-title":"Int Immunol"},{"key":"2021120808392188700_cei13147-bib-0016","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/0090-1229(85)90153-9","article-title":"Interaction of mutant lpr gene with background strain influences renal disease","volume":"37","author":"Kelley","year":"1985","journal-title":"Clin Immunol Immunopathol"},{"key":"2021120808392188700_cei13147-bib-0017","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1136\/ard.62.6.556","article-title":"Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis","volume":"62","author":"Alba","year":"2003","journal-title":"Ann Rheum Dis"},{"key":"2021120808392188700_cei13147-bib-0018","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1093\/rheumatology\/keh656","article-title":"Induction of systemic lupus erythematosus-like syndrome in syngeneic mice by immunization with activated lymphocyte-derived DNA","volume":"44","author":"Qiao","year":"2005","journal-title":"Rheumatology (Oxf)"},{"key":"2021120808392188700_cei13147-bib-0019","doi-asserted-by":"crossref","first-page":"6465","DOI":"10.4049\/jimmunol.0904016","article-title":"Blockade of Notch1 signaling alleviates murine lupus via blunting macrophage activation and M2b polarization","volume":"184","author":"Zhang","year":"2010","journal-title":"J Immunol"},{"key":"2021120808392188700_cei13147-bib-0020","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.4049\/jimmunol.1002315","article-title":"Macrophage differentiation and polarization via phosphatidylinositol 3-kinase\/Akt-ERK signaling pathway conferred by serum amyloid P component","volume":"187","author":"Zhang","year":"2011","journal-title":"J Immunol"},{"key":"2021120808392188700_cei13147-bib-0021","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.molimm.2015.01.023","article-title":"Extracellular, but not intracellular HMGB1, facilitates self-DNA induced macrophage activation via promoting DNA accumulation in endosomes and contributes to the pathogenesis of lupus nephritis","volume":"65","author":"Li","year":"2015","journal-title":"Mol Immunol"},{"key":"2021120808392188700_cei13147-bib-0022","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1177\/0961203311434940","article-title":"Production of anti-double-stranded DNA antibodies in activated lymphocyte derived DNA induced lupus model was dependent on CD4+ T cells","volume":"21","author":"Wen","year":"2012","journal-title":"Lupus"},{"key":"2021120808392188700_cei13147-bib-0023","doi-asserted-by":"crossref","first-page":"e58161","DOI":"10.1371\/journal.pone.0058161","article-title":"Interleukin-17 expression positively correlates with disease severity of lupus nephritis by increasing anti-double-stranded DNA antibody production in a lupus model induced by activated lymphocyte derived DNA","volume":"8","author":"Wen","year":"2013","journal-title":"PLOS ONE"},{"key":"2021120808392188700_cei13147-bib-0024","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/ni.1610","article-title":"The differentiation of human TH-17 cells requires transforming growth factor-[beta] and induction of the nuclear receptor ROR[gamma]t","volume":"9","author":"Manel","year":"2008","journal-title":"Nat Immunol"},{"key":"2021120808392188700_cei13147-bib-0025","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/ni1488","article-title":"IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways","volume":"8","author":"Zhou","year":"2007","journal-title":"Nat Immunol"},{"key":"2021120808392188700_cei13147-bib-0026","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nature05970","article-title":"IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells","volume":"448","author":"Korn","year":"2007","journal-title":"Nature"},{"key":"2021120808392188700_cei13147-bib-0027","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nature10957","article-title":"Pathogen-induced human TH17 cells produce IFN-[ggr] or IL-10 and are regulated by IL-1[bgr]","volume":"484","author":"Zielinski","year":"2012","journal-title":"Nature"},{"key":"2021120808392188700_cei13147-bib-0028","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.clim.2016.09.002","article-title":"Anti-dsDNA antibodies and resident renal cells \u2013 their putative roles in pathogenesis of renal lesions in lupus nephritis","volume":"185","author":"Yung","year":"2017","journal-title":"Clin Immunol"},{"key":"2021120808392188700_cei13147-bib-0029","first-page":"227","article-title":"Experimental use of murine lupus models","volume":"102","author":"Peng","year":"2004","journal-title":"Methods Mol Med"},{"key":"2021120808392188700_cei13147-bib-0030","first-page":"645","article-title":"Ipr gene control of the anti-DNA antibody response","volume":"19","author":"Pisetsky","year":"1982","journal-title":"J Immunol"},{"key":"2021120808392188700_cei13147-bib-0031","doi-asserted-by":"crossref","first-page":"227","DOI":"10.4049\/jimmunol.133.1.227","article-title":"Induction of various autoantibodies by mutant gene lpr in several strains of mice","volume":"133","author":"Izui","year":"1984","journal-title":"J Immunol"},{"key":"2021120808392188700_cei13147-bib-0032","doi-asserted-by":"crossref","first-page":"9970","DOI":"10.1073\/pnas.0603912103","article-title":"A Tlr7 translocation accelerates systemic autoimmunity in murine lupus","volume":"103","author":"Subramanian","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021120808392188700_cei13147-bib-0033","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1002\/eji.200838138","article-title":"Yaa autoimmune phenotypes are conferred by overexpression of TLR7","volume":"38","author":"Fairhurst","year":"2008","journal-title":"Eur J Immunol"},{"key":"2021120808392188700_cei13147-bib-0034","doi-asserted-by":"crossref","first-page":"38619","DOI":"10.1038\/srep38619","article-title":"Nuclear factor erythroid 2-related factor 2 deficiency exacerbates lupus nephritis in B6\/lpr mice by regulating Th17 cell function","volume":"6","author":"Zhao","year":"2016","journal-title":"Sci Rep"},{"key":"2021120808392188700_cei13147-bib-0035","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1177\/0961203310389100","article-title":"IL-17-producing T cells in lupus nephritis","volume":"20","author":"Apostolidis","year":"2011","journal-title":"Lupus"},{"key":"2021120808392188700_cei13147-bib-0036","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3389\/fimmu.2015.00610","article-title":"Disturbed T cell signaling and altered Th17 and regulatory T cell subsets in the pathogenesis of systemic lupus erythematosus","volume":"6","author":"Rother","year":"2015","journal-title":"Front Immunol"},{"key":"2021120808392188700_cei13147-bib-0037","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/BOR.0b013e328304b6b5","article-title":"IL-17 and the Th17 lineage in systemic lupus erythematosus","volume":"20","author":"Garrett-Sinha","year":"2008","journal-title":"Curr Opin Rheumatol"},{"key":"2021120808392188700_cei13147-bib-0038","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2006.07.035","article-title":"The orphan nuclear receptor ROR\u03b3t directs the differentiation program of proinflammatory IL-17+ T helper cells","volume":"126","author":"Ivanov","year":"2006","journal-title":"Cell"},{"key":"2021120808392188700_cei13147-bib-0039","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.immuni.2006.01.001","article-title":"TGF\u03b2 in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells","volume":"24","author":"Veldhoen","year":"2006","journal-title":"Immunity"},{"key":"2021120808392188700_cei13147-bib-0040","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/ni1539","article-title":"TGF-[beta] and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology","volume":"8","author":"McGeachy","year":"2007","journal-title":"Nat Immunol"},{"key":"2021120808392188700_cei13147-bib-0041","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/nature09447","article-title":"Generation of pathogenic TH17 cells in the absence of TGF-[bgr] signalling","volume":"467","author":"Ghoreschi","year":"2010","journal-title":"Nature"},{"key":"2021120808392188700_cei13147-bib-0042","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nrrheum.2011.1","article-title":"Long-lived autoreactive plasma cells drive persistent autoimmune inflammation","volume":"7","author":"Hiepe","year":"2011","journal-title":"Nat Rev Rheumatol"},{"key":"2021120808392188700_cei13147-bib-0043","doi-asserted-by":"crossref","first-page":"5671","DOI":"10.4049\/jimmunol.176.9.5671","article-title":"Neonatal immunization with a Sindbis virus-DNA measles vaccine induces adult-like neutralizing antibodies and cell-mediated immunity in the presence of maternal antibodies","volume":"176","author":"Capozzo","year":"2006","journal-title":"J Immunol"},{"key":"2021120808392188700_cei13147-bib-0044","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1172\/JCI111959","article-title":"Detection of cross-reactive anti-DNA antibody idiotypes on renal tissue-bound immunoglobulins from lupus patients","volume":"76","author":"Isenberg","year":"1985","journal-title":"J Clin Invest"},{"key":"2021120808392188700_cei13147-bib-0045","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3109\/08916930903374600","article-title":"Autoantibody-dependent and autoantibody-independent roles for B cells in systemic lupus erythematosus: past, present, and future","volume":"43","author":"Jacob","year":"2010","journal-title":"Autoimmunity"},{"key":"2021120808392188700_cei13147-bib-0046","doi-asserted-by":"crossref","first-page":"E2797","DOI":"10.1073\/pnas.1402159111","article-title":"Activation of Ras overcomes B-cell tolerance to promote differentiation of autoreactive B cells and production of autoantibodies","volume":"111","author":"Teodorovic","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021120808392188700_cei13147-bib-0047","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/ni1552","article-title":"Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice","volume":"9","author":"Hsu","year":"2008","journal-title":"Nat Immunol"},{"key":"2021120808392188700_cei13147-bib-0048","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/ni.1741","article-title":"Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus","volume":"10","author":"Doreau","year":"2009","journal-title":"Nat Immunol"},{"key":"2021120808392188700_cei13147-bib-0049","doi-asserted-by":"crossref","first-page":"e8474","DOI":"10.1371\/journal.pone.0008474","article-title":"Anti-dsDNA antibodies promote initiation, and acquired loss of renal Dnase1 promotes progression of lupus nephritis in autoimmune (NZBxNZW)F1 mice","volume":"4","author":"Fenton","year":"2009","journal-title":"PLOS ONE"},{"key":"2021120808392188700_cei13147-bib-0050","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1191\/0961203305lu2054oa","article-title":"Pathogenic autoantibodies in lupus nephritis","volume":"14","author":"Waldman","year":"2005","journal-title":"Lupus"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.13147","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/193\/3\/302\/41645569\/cei13147.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/193\/3\/302\/41645569\/cei13147.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T09:58:54Z","timestamp":1693648734000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/193\/3\/302\/6411932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,23]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,7,23]]},"published-print":{"date-parts":[[2018,9,21]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.13147","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"type":"print","value":"0009-9104"},{"type":"electronic","value":"1365-2249"}],"subject":[],"published-other":{"date-parts":[[2018,9]]},"published":{"date-parts":[[2018,7,23]]}}}