{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:25:48Z","timestamp":1788326748883,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T00:00:00Z","timestamp":1538006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Singapore Immunology Network, Agency for Science, Technology, and Research"},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"Objective<\/jats:title>Toll\u2010like receptors (TLR<\/jats:styled-content>s) 7 and 9 are important innate signaling molecules with opposing roles in the development and progression of systemic lupus erythematosus (SLE<\/jats:styled-content>). While multiple studies support the notion of a dependency on TLR<\/jats:styled-content>\u20107 for disease development, genetic ablation of TLR<\/jats:styled-content>\u20109 results in severe disease with glomerulonephritis (GN<\/jats:styled-content>) by a largely unknown mechanism. This study was undertaken to examine the suppressive role of TLR<\/jats:styled-content>\u20109 in the development of severe lupus in a mouse model.<\/jats:p><\/jats:sec>Methods<\/jats:title>We crossed Sle1<\/jats:italic> lupus\u2010prone mice with TLR<\/jats:styled-content>\u20109\u2013deficient mice to generate Sle1<\/jats:italic>TLR<\/jats:styled-content>\u20109\u2212\/\u2212<\/jats:sup> mice. Mice ages 4.5\u20136.5 months were evaluated for severe autoimmunity by assessing splenomegaly, GN<\/jats:styled-content>, immune cell populations, autoantibody and total Ig profiles, kidney dendritic cell (DC<\/jats:styled-content>) function, and TLR<\/jats:styled-content>\u20107 protein expression. Mice ages 8\u201310 weeks were used for functional B cell studies, Ig profiling, and determination of TLR<\/jats:styled-content>\u20107 expression.<\/jats:p><\/jats:sec>Results<\/jats:title>Sle1<\/jats:italic>TLR<\/jats:styled-content>\u20109\u2212\/\u2212<\/jats:sup> mice developed severe disease similar to TLR<\/jats:styled-content>\u20109\u2013deficient MRL<\/jats:styled-content><\/jats:italic> and Nba2<\/jats:italic> models. Sle1<\/jats:italic>TLR<\/jats:styled-content>\u20109\u2212\/\u2212<\/jats:sup> mouse B cells produced more class\u2010switched antibodies, and the autoantibody repertoire was skewed toward RNA<\/jats:styled-content>\u2010containing antigens. GN<\/jats:styled-content> in these mice was associated with DC<\/jats:styled-content> infiltration, and purified Sle1<\/jats:italic>TLR<\/jats:styled-content>\u20109\u2212\/\u2212<\/jats:sup> mouse renal DC<\/jats:styled-content>s were more efficient at TLR<\/jats:styled-content>\u20107\u2013dependent antigen presentation and expressed higher levels of TLR<\/jats:styled-content>\u20107 protein. Importantly, this increase in TLR<\/jats:styled-content>\u20107 expression occurred prior to disease development, indicating a role in the initiation stages of tissue destruction.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The increase in TLR<\/jats:styled-content>\u20107\u2013reactive immune complexes, and the concomitant enhanced expression of their receptor, promotes inflammation and disease in Sle1<\/jats:italic>TLR<\/jats:styled-content>9\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40535","type":"journal-article","created":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T03:04:49Z","timestamp":1524539089000},"page":"1597-1609","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Toll\u2010Like Receptor 9 Deficiency Breaks Tolerance to RNA\u2010Associated Antigens and Up\u2010Regulates Toll\u2010Like Receptor 7 Protein in Sle1<\/i> Mice"],"prefix":"10.1002","volume":"70","author":[{"given":"Teja","family":"Celhar","sequence":"first","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology, and Research Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Yasuga","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology, and Research Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Yin","family":"Lee","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology, and Research Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Zharkova","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology, and Research Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubhita","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology, and Research Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susannah I.","family":"Thornhill","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology, and Research Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao K.","family":"Lu","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology, and Research Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijin","family":"Au","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology Agency for Science, Technology, and Research Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina H. 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