Abstract
Systemic lupus erythematosus is characterized by the production of autoantibodies directed against nuclear Ags, including nucleosome and DNA. TLR9 is thought to play a role in the production of these autoantibodies through the capacity of nuclear immunogenic particles to interact both with BCR and TLR9. To determine the role of TLR9 in SLE, C57BL/6-lpr/lpr-TLR9(-/-) and TLR9(+/+) mice were analyzed. The abrogation of TLR9 totally impaired the production of anti-nucleosome Abs, whereas no difference was observed in the frequency of anti-dsDNA autoantibodies whose titer was strikingly higher in TLR9(-/-) mice. In addition a higher rate of mesangial proliferation was observed in the kidney of TLR9-deficient animals. These results indicate that in C57BL/6-lpr/lpr mice, TLR9 is absolutely required for the anti-nucleosome Ab response but not for anti-dsDNA Ab production which is involved in mesangial proliferation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Antinuclear / biosynthesis*
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Antibodies, Antinuclear / blood
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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Chromatin / immunology
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CpG Islands / immunology
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DNA / immunology*
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DNA, Single-Stranded / immunology
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Glomerular Mesangium / immunology
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Glomerular Mesangium / pathology
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Immunophenotyping
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Lupus Nephritis / genetics*
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Lupus Nephritis / immunology*
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Lupus Nephritis / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Inbred MRL lpr
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Mice, Knockout
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Mutation*
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Nucleosomes / immunology*
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Oligodeoxyribonucleotides / administration & dosage
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Oligodeoxyribonucleotides / immunology
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Proteinuria / genetics
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Proteinuria / immunology
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Rheumatoid Factor / biosynthesis
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Rheumatoid Factor / blood
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Toll-Like Receptor 9 / deficiency
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Toll-Like Receptor 9 / genetics
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Toll-Like Receptor 9 / metabolism
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Toll-Like Receptor 9 / physiology*
Substances
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Antibodies, Antinuclear
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CPG-oligonucleotide
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Chromatin
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DNA, Single-Stranded
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Nucleosomes
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Oligodeoxyribonucleotides
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Tlr9 protein, mouse
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Toll-Like Receptor 9
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DNA
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Rheumatoid Factor