Role of TLR9 in Anti-Nucleosome and Anti-DNA Antibody Production in lpr Mutation-Induced Murine Lupus

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 T...

Full description

Saved in:
Bibliographic Details
Published in:Journal of Immunology 2006-07, Vol.177 (2), p.1349-1354
Main Authors: Lartigue, Aurelia, Courville, Philippe, Auquit, Isabelle, Francois, Arnaud, Arnoult, Christophe, Tron, Francois, Gilbert, Daniele, Musette, Philippe
Format: Article
Language:English
Subjects:
Animals
Antibodies, Antinuclear - biosynthesis
Antibodies, Antinuclear - blood
B-Lymphocyte Subsets - immunology
B-Lymphocyte Subsets - metabolism
Chromatin - immunology
CpG Islands - immunology
DNA - immunology
DNA, Single-Stranded - immunology
Glomerular Mesangium - immunology
Glomerular Mesangium - pathology
Immunophenotyping
Lupus Nephritis - genetics
Lupus Nephritis - immunology
Lupus Nephritis - pathology
Mice
Mice, Inbred C57BL
Mice, Inbred MRL lpr
Mice, Knockout
Mutation
Nucleosomes - immunology
Oligodeoxyribonucleotides - administration & dosage
Oligodeoxyribonucleotides - immunology
Proteinuria - genetics
Proteinuria - immunology
Rheumatoid Factor - biosynthesis
Rheumatoid Factor - blood
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
Toll-Like Receptor 9 - deficiency
Toll-Like Receptor 9 - genetics
Toll-Like Receptor 9 - metabolism
Toll-Like Receptor 9 - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.177.2.1349