Document Detail

Critical role of TLR2 and TLR4 in autoantibody production and glomerulonephritis in lpr mutation-induced mouse lupus.
MedLine Citation:
PMID:  19841185     Owner:  NLM     Status:  MEDLINE    
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathogenic autoantibodies directed against nuclear Ags and immune complex deposits in damaged organs. Environmental factors have been thought to play a role in the onset of the disease. The recognition of these factors is mediated by TLRs, in particular TLR2 and TLR4 which bind pathogen-associated molecular patterns of Gram(+) and Gram(-) bacteria, respectively. We attempted to determine the role of these TLRs in SLE by creating TLR2- or TLR4-deficient C57BL/6(lpr/lpr) mice. These mice developed a less severe disease and fewer immunological alterations. Indeed, in C57BL/6(lpr/lpr)-TLR2 or -TLR4-deficient mice, glomerular IgG deposits and mesangial cell proliferation were dramatically decreased and antinuclear, anti-dsDNA, and anti-cardiolipin autoantibody titers were significantly reduced. However, the response against nucleosome remained unaffected, indicating a role of TLR2 and TLR4 in the production of Abs directed against only certain categories of SLE-related autoantigens. Analysis of B cell phenotype showed a significant reduction of marginal zone B cells, particularly in C57BL/6(lpr/lpr)-TLR4-deficient mice, suggesting an important role of TLR4 in the sustained activation of these cells likely involved in autoantibody production. Interestingly, the lack of TLR4 also affected the production of cytokines involved in the development of lupus disease.
Aurelia Lartigue; Natacha Colliou; Sébastien Calbo; Arnault François; Serge Jacquot; Christophe Arnoult; Francois Tron; Daniele Gilbert; Philippe Musette
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-19
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  183     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-05     Completed Date:  2009-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6207-16     Citation Subset:  AIM; IM    
INSERM, Unité 905, Rouen, France.
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MeSH Terms
Antibodies, Antinuclear / biosynthesis,  blood
Autoantibodies / biosynthesis*,  blood
Autoimmune Diseases / genetics,  immunology,  metabolism,  pathology
B-Lymphocyte Subsets / immunology*,  metabolism
Cytokines / immunology,  metabolism
Glomerulonephritis / genetics,  immunology*,  metabolism,  pathology
Immunoglobulin G / blood
Lupus Erythematosus, Systemic / genetics,  immunology*,  metabolism,  pathology
Mice, Inbred MRL lpr
Mice, Knockout
Mice, Mutant Strains
Mutation / genetics,  immunology
Toll-Like Receptor 2 / genetics,  immunology*,  metabolism
Toll-Like Receptor 4 / genetics,  immunology*,  metabolism
Reg. No./Substance:
0/Antibodies, Antinuclear; 0/Autoantibodies; 0/Cytokines; 0/Immunoglobulin G; 0/Tlr2 protein, mouse; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4

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