Critical role of TLR7 in the acceleration of systemic lupus erythematosus in TLR9-deficient mice

Marie Laure Santiago-Raber, Isabelle Dunand-Sauthier, Tianfu Wu, Quan Zhen Li, Satoshi Uematsu, Shizuo Akira, Walter Reith, Chandra Mohan, Brian L. Kotzin, Shozo Izui

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

Accumulating evidence supports the idea that TLR7 and TLR9 play pathogenic and protective roles, respectively, in the development of murine systemic lupus erythematosus (SLE). However, the molecular mechanism responsible for the accelerated development of SLE resulting from the deletion of TLR9 and the respective contributions of TLR7 and TLR9 to the development of different autoimmune responses against nuclear and non-nuclear autoantigens implicated in lupus nephritis have not been well defined. In the present study, we addressed these questions by assessing the effect of the TLR9 and/or TLR7 deletion on the production of various autoantibodies and the development of lupus nephritis in C57BL/6 mice congenic for the Nba2 (NZB autoimmunity 2) locus (B6.Nba2). TLR9-deficient B6.Nba2 mice displayed increased production of autoantibodies against nuclear antigens, serum retroviral gp70 and glomerular matrix antigens, and developed a markedly accelerated form of lupus nephritis. Enhanced disease was associated with functionally upregulated expression of TLR7, as documented by an increased TLR7-dependent activation of B cells and plasmacytoid dendritic cells. Notably, disease exacerbation in TLR9-deficient mice was completely suppressed by the deletion of TLR7. Our results indicate that TLR7 has a pivotal role in a wide variety of autoimmune responses against DNA- and RNA-containing nuclear antigens, retroviral gp70 and glomerular matrix antigens implicated in murine SLE, and that enhanced TLR7 activity is critical for the accelerated development of SLE in TLR9-deficient lupus-prone mice.

Original languageEnglish (US)
Pages (from-to)339-348
Number of pages10
JournalJournal of Autoimmunity
Volume34
Issue number4
DOIs
StatePublished - Jun 2010

Keywords

  • Endogenous retrovirus
  • Lupus nephritis
  • Systemic lupus erythematosus
  • Toll-like receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Critical role of TLR7 in the acceleration of systemic lupus erythematosus in TLR9-deficient mice'. Together they form a unique fingerprint.

Cite this