{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T11:25:13Z","timestamp":1789903513839,"version":"4.0.1"},"reference-count":34,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"published-print":{"date-parts":[[2014]]},"abstract":"<b><i>Background:<\/i><\/b> Toll-like receptor-7 (TLR7), which recognizes viral single-stranded RNA, can trigger immune complex glomerulonephritis in experimental lupus erythematosus. However, whether it modulates dendritic cells (DCs) phenotype and regulatory T cells (Treg) function is incompletely understood. <b><i>Method:<\/i><\/b> Splenocytes and bone marrow DCs were obtained from 5- and 20-week-old female MRL<sup>lpr\/lpr<\/sup> mice and C57BL\/6 mice. In addition, to understand the response of Treg and DCs to TLR7 ligation in vivo, 16-week-old female MRL<sup>lpr\/lpr<\/sup> and C57BL\/6 mice were distributed into two groups with or without intraperitoneal injections of TLR7 ligand every other day. <b><i>Results:<\/i><\/b> After activation with the TLR7 ligand imiquimod in vivo and vitro, DCs from imiquimod-treated MRL\/lpr mice showed an altered costimulatory profile, with decreased induction of CD80, CD86, and MHCII expression, comparing to age-matched C57BL\/6 control mice. There was no significant difference in the numbers of CD<sub>4<\/sub><sup>+<\/sup>CD<sub>25<\/sub><sup>+<\/sup>Foxp3<sup>+<\/sup> cells after TLR7 ligation by imiquimod in MRL<sup>lpr\/lpr<\/sup> and control mice. Immunostaining of kidney sections of nephritic MRL\/lpr mice revealed that CD11c was expressed in the infiltrated tubulointerstitial cells, and confocal microscopic analysis of renal CD11c<sup>+<\/sup>MHCII<sup>+<\/sup>, CD11c<sup>+<\/sup>CD80<sup>+<\/sup>, and CD11c<sup>+&#x200B;<\/sup>CD86<sup>+<\/sup> cells showed an immature phenotype with low levels of CD80, CD86, and MHCII in imiquimod-treated MRL\/lpr mice. There was no difference in the number of Foxp3 positive cells in kidneys between the imiq\u2011uimod and vehicle-treated groups. <b><i>Conclusions:<\/i><\/b> Our results suggest that activation of TLR7 exacerbated lupus nephritis by modulating the abnormally costimulatory phenotype of dendritic cells and functions of Treg in MRL\/lpr mice.<\/jats:p>","DOI":"10.1159\/000368204","type":"journal-article","created":{"date-parts":[[2014,10,21]],"date-time":"2014-10-21T08:14:56Z","timestamp":1413879296000},"page":"325-344","source":"Crossref","is-referenced-by-count":16,"title":["Activation of Toll-like Receptor-7 Exacerbates Lupus Nephritis by Modulating Regulatory T Cells"],"prefix":"10.1159","volume":"40","author":[{"given":"Li","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanzhan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiLi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Feng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2014,10,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0502-423"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/ni712"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1122545"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/32588"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/ni0901-816"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/nri1957"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1186\/ar3018"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1186\/ar3075"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1999.00452.x"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-007-0096-x"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00453.2005"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.09.009"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838138"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005070714"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0908559"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007030273"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/ni1289"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25439"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601554103"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.6.3712"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021633"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.8051"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113401"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021633"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25439"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28423"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1126\/science.1078231"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-009-0218-y"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2007.01.014"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.2.944"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.1.271"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2006.09.007"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1080\/08830180500544480"}],"container-title":["American 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