Activation of toll-like receptor-7 exacerbates lupus nephritis by modulating regulatory T cells.

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 MRLIpr/Ipr mice and C57BL/6 mice. In addition, to understand the response of Treg and DCs to TLR7 ligation in vivo, 16-week-old female MRLIpr/Ipr 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/Ipr 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(4)(+)CD(25)(+)Foxp3(+) cells after TLR7 ligation by imiquimod in MRLIpr/Ipr and control mice. Immunostaining of kidney sections of nephritic MRL/Ipr 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/Ipr mice. There was no difference in the number of Foxp3 positive cells in kidneys between the imiq-uimod 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/Ipr mice. (C) 2014S. Karger AG, Basel