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  • Title: Activation of toll-like receptor-7 exacerbates lupus nephritis by modulating regulatory T cells.
    Author: Gong L, Wang Y, Zhou L, Bai X, Wu S, Zhu F, Zhu YF.
    Journal: Am J Nephrol; 2014; 40(4):325-44. PubMed ID: 25341693.
    Abstract:
    BACKGROUND: 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. METHOD: Splenocytes and bone marrow DCs were obtained from 5- and 20-week-old female MRL(lpr/lpr) 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(lpr/lpr) and C57BL/6 mice were distributed into two groups with or without intraperitoneal injections of TLR7 ligand every other day. RESULTS: 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 CD4+CD25+Foxp3+ cells after TLR7 ligation by imiquimod in MRL(lpr/lpr) 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+MHCII+, CD11c+CD80+, and CD11c+)CD86+ 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 imiquimod and vehicle-treated groups. CONCLUSIONS: 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.
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