Role of TLR9 in anti-nucleosome and anti-DNA antibody production in lpr mutation-induced murine lupus.

Full 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.

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Author information

Author/s: Lartigue, Aurelia (A); Courville, Philippe (P); Auquit, Isabelle (I); François, Arnaud (A); Arnoult, Christophe (C); Tron, François (F); Gilbert, Daniele (D); Musette, Philippe (P);

Affiliation: Institut National de la Santé et de la Recherche Médicale Unité 519 and Institut Fédératif de Recherche Multidisciplinaire sur les Peptides, Faculté de Médecine et Pharmacie, 22 boulevard Gambetta, 76183 Rouen Cedex, France.

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol), published in United States. (Language: eng)

Reference: 2006-Jul; vol 177 (issue 2) : pp 1349-54

Dates: Created 2006/07/04; Completed 2006/08/18; Revised 2006/11/15;

PMID: 16818796, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Antibodies, Antinuclear - biosynthesis; blood
B-Lymphocyte Subsets - immunology; metabolism
Chromatin - immunology
CpG Islands - immunology
DNA - immunology
DNA, Single-Stranded - immunology
Glomerular Mesangium - immunology; pathology
Immunophenotyping
Lupus Nephritis - genetics; immunology; pathology
Mice

Mice
Mice, Inbred C57BL
Mice, Inbred MRL lpr
Mice, Knockout
Mutation
Nucleosomes - immunology
Oligodeoxyribonucleotides - administration & dosage; immunology
Proteinuria - genetics; immunology
Rheumatoid Factor - biosynthesis; blood
T-Lymphocyte Subsets - immunology; metabolism
Toll-Like Receptor 9 - deficiency; genetics; metabolism; physiology

Associated Chemicals: Antibodies, Antinuclear (0) ; CPG-oligonucleotide (0) ; Chromatin (0) ; DNA, Single-Stranded (0) ; Nucleosomes (0) ; Oligodeoxyribonucleotides (0) ; Tlr9 protein, mouse (0) ; Toll-Like Receptor 9 (0) ; DNA (9007-49-2) ; Rheumatoid Factor (9009-79-4)

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