Role of TLR9 in Anti-Nucleosome and Anti-DNA Antibody Production in lpr Mutation-Induced Murine Lupus
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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SLE has been linked to TLR9 overstimulation by self DNA.
“MAS is recognized also as a complication of systemic lupus erythematosus (34), a disease that has been linked to TLR9 overstimulation by self DNA (35)(36)(37)(38).”
From Repeated TLR9 stimulation results in macrophage activation syndrome–like disease in mice (2011) · cites this paper as [37]
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References 44 · Cited by 165
- Authors
- Lartigue, A., Courville, P., Auquit, I., François, A., Arnoult, C., Tron, F., Gilbert, D., & Musette, P.
- Affiliations
- 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 , Rouen ,
- Inserm (FR)
- Laboratoire d’Anatomie-Pathologique, Centre Hospitalier Universitaire Charles Nicolle , Rouen ,
- ORCID
- Arnoult, Christophe
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-07
- Volume
- 177
- Issue
- 2
- Pages
- 1349-1354
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2161093494
- Cited by
- 165
- References
- 44
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 9 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 12 · 2016: 5 · 2015: 12 · 2014: 8 · 2013: 10 · 2012: 10
- FWCI
- 11.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- TLR9, systemic lupus erythematosus, anti-nucleosome antibodies, anti-dsDNA antibodies, autoantibody production, lpr mutation, mesangial cell proliferation, kidney, TLR9-deficient mice
- MeSH terms
- Animals, Antibodies, Antinuclear, Chromatin, DNA, DNA, Single-Stranded, Glomerular Mesangium, Lupus Nephritis, Mice, Inbred C57BL, Mutation, Nucleosomes, Oligodeoxyribonucleotides, Proteinuria, Rheumatoid Factor, Immunophenotyping, B-Lymphocyte Subsets, T-Lymphocyte Subsets, Mice, Knockout, CpG Islands, Mice, Inbred MRL lpr, Toll-Like Receptor 9, Mice
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