{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:47:02Z","timestamp":1780591622766,"version":"3.54.1"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T00:00:00Z","timestamp":1369872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The mechanisms involved in breaking immunologic tolerance against nuclear autoantigens in systemic lupus erythematosus (SLE) are not fully understood. Our recent studies in nonautoimmune mice provided evidence of an important role of Toll\u2010like receptor 2 (TLR\u20102) in antichromatin autoantibody induction by high mobility group box chromosomal protein 1\u2013nucleosome complexes derived from apoptotic cells. The objective of this study was to investigate whether TLR\u20102 signaling is required for the induction of autoantibodies and the development of SLE\u2010like disease in murine pristane\u2010induced lupus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lupus\u2010like disease in C57BL\/6 and TLR\u20102<jats:sup>\u2212\/\u2212<\/jats:sup> mice was induced by pristane injection. The numbers of immune cells and serum cytokine concentrations were determined by flow cytometry. Renal disease was assessed by quantification of proteinuria, histologic analyses, and enzyme\u2010linked immunospot assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pristane\u2010injected TLR\u20102<jats:sup>\u2212\/\u2212<\/jats:sup> mice generated reduced numbers of splenic CD138+\/cytoplasmic \u03baL\/\u03bbL chain\u2013positive plasma cells and displayed diminished IgG responses against double\u2010stranded DNA, histones, nucleosomes, some extractable nuclear autoantigens, and cardiolipin when compared with wild\u2010 type controls. TLR\u20102 deficiency prevented the pristane\u2010induced systemic release of interleukin\u20106 (IL\u20106) and IL\u201010. The absence of TLR\u20102 attenuated peritoneal recruitment of CD11c+ cells and formation of lipogranulomas. Importantly, the renal disease that developed in pristane\u2010treated TLR\u20102<jats:sup>\u2212\/\u2212<\/jats:sup> mice was less severe than that in control mice, as reflected by milder proteinuria, reduced glomerular deposition of IgG and complement, and decreased renal infiltration of autoantibody\u2010secreting cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TLR\u20102 is required for the production of prototypical lupus autoantibodies and the development of renal disease in pristane\u2010induced murine lupus. Interference with TLR\u20102 signaling may be a promising novel strategy for the treatment of SLE.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37914","type":"journal-article","created":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T11:33:30Z","timestamp":1362137610000},"page":"1612-1623","source":"Crossref","is-referenced-by-count":43,"title":["Toll\u2010like Receptor 2 Is Required for Autoantibody Production and Development of Renal Disease in Pristane\u2010Induced Lupus"],"prefix":"10.1002","volume":"65","author":[{"given":"Vilma","family":"Urbonaviciute","sequence":"first","affiliation":[{"name":"University Hospital Erlangen and University of Erlangen\u2013Nuremberg Erlangen Germany"},{"name":"Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Starke","sequence":"additional","affiliation":[{"name":"University Hospital Erlangen and University of Erlangen\u2013Nuremberg Erlangen 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