title: Activation of toll-like receptor-7 exacerbates lupus nephritis by modulating regulatory T cells.
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.
  
  
  METHODS
  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.
authors.affiliation: Experimental animal center, Nanfang Hospital, Southern Medical University, Guang Zhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.forename: Yuanzhan
authors.initials: Y
authors.lastname: Wang
authors.forename: LiLi
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Bai
authors.forename: Sha
authors.initials: S
authors.lastname: Wu
authors.forename: Fengxin
authors.initials: F
authors.lastname: Zhu
authors.forename: Yu Feng
authors.initials: YF
authors.lastname: Zhu
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D000077271:Imiquimod; D007668:Kidney / Q000473:pathology; D008024:Ligands; D008181:Lupus Nephritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D008024:Ligands; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D000077271:Imiquimod