{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:15:04Z","timestamp":1791296104236,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,4,27]],"date-time":"2007-04-27T00:00:00Z","timestamp":1177632000000},"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":[[2007,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Toll\u2010like receptor 9 (TLR\u20109), a receptor for CpG DNA, has been implicated in the activation of immune cells in lupus. We undertook this study to determine whether the expression of TLR\u20109 in resident renal cells in lupus nephritis is related to the development of tubulointerstitial injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>TLR\u20109 was analyzed in selectively retrieved renal tissue from (NZB \u00d7 NZW)F<jats:sub>1<\/jats:sub> mice at different stages of disease by laser capture microdissection combined with real\u2010time quantitative reverse transcriptase\u2013polymerase chain reaction, and in renal biopsy specimens from lupus nephritis patients by immunohistochemistry. We investigated for the molecular component responsible for TLR\u20109 activation by cultured proximal tubular cells in serum from patients with lupus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Renal tissue from NZB \u00d7 NZW mice displayed robust TLR\u20109 expression localized to proximal tubular cells. TLR\u20109 levels correlated with proteinuria and tubulointerstitial injury to the extent that a cyclin\u2010dependent kinase inhibitor, while reducing proteinuria and renal structural damage, prevented tubular TLR\u20109 generation in lupus mice. Consistently, exaggerated TLR\u20109 staining was found in proximal tubular cells of lupus patients, which correlated with tubulointerstitial damage. DNA\u2010containing immune complexes purified from sera of patients with lupus induced TLR\u20109 in cultured proximal tubular cells. This was prevented by CCGG\u2010rich short oligonucleotides, specific antagonists of CpG DNA, indicating that the DNA component of immune complexes was required for TLR\u20109 stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that tubular TLR\u20109 activation has a pathogenetic role in tubulointerstitial inflammation and damage in experimental and human lupus nephritis, and they indicate a novel target for future therapies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22524","type":"journal-article","created":{"date-parts":[[2007,4,27]],"date-time":"2007-04-27T20:50:12Z","timestamp":1177707012000},"page":"1569-1578","source":"Crossref","is-referenced-by-count":62,"title":["Involvement of renal tubular toll\u2010like receptor 9 in the development of tubulointerstitial injury in systemic 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