Document Detail

Toll-like receptor 9-independent aggravation of glomerulonephritis in a novel model of SLE.
MedLine Citation:
PMID:  16798839     Owner:  NLM     Status:  MEDLINE    
The generation of anti-DNA auto-antibodies is characteristic for the human autoimmune condition systemic lupus erythematosus (SLE) and its animal models. However, the contribution of the toll-like receptor (TLR) system of innate immunity receptors and, in particular, TLR9 to this B cell-mediated autoimmune process remains controversial. Here we report that in a novel murine model of SLE, based on hyper-reactive B cell activation mediated by mutant phospholipase Cg2, the genetic deficiency of TLR9 does not protect from spontaneous anti-DNA auto-antibody formation and glomerulonephritis. On the contrary, disease induction is aggravated and additional nucleolar antibody specificity develops in autoimmune TLR9-deficient mice. In vitro studies demonstrate that, in autoimmune-prone mice, dual signaling via the B cell receptor and non-CpG DNA results in synergistic B cell activation in a TLR9-independent manner. These results suggest that engagement of a TLR9-independent DNA activation pathway may promote autoimmunity, while TLR9 signaling can ameliorate SLE-like immune pathology in vivo.
Philipp Yu; Ute Wellmann; Sandra Kunder; Leticia Quintanilla-Martinez; Luise Jennen; Neil Dear; Kerstin Amann; Stefan Bauer; Thomas H Winkler; Hermann Wagner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-23
Journal Detail:
Title:  International immunology     Volume:  18     ISSN:  0953-8178     ISO Abbreviation:  Int. Immunol.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-13     Completed Date:  2006-09-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8916182     Medline TA:  Int Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1211-9     Citation Subset:  IM    
Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstrasse 4a, 81675 Munich, Germany.
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MeSH Terms
Antibodies, Antinuclear / biosynthesis,  immunology
Autoantibodies / biosynthesis,  immunology
B-Lymphocytes / immunology
DNA / immunology
Disease Models, Animal
Glomerulonephritis / enzymology,  genetics,  immunology*
Lupus Erythematosus, Systemic / blood,  enzymology,  genetics,  immunology*
Lymphocyte Activation
Mice, Inbred C3H
Mice, Inbred C57BL
Phospholipase C gamma / genetics,  immunology
Splenomegaly / immunology
Toll-Like Receptor 9 / deficiency,  genetics,  immunology*
Reg. No./Substance:
0/Antibodies, Antinuclear; 0/Autoantibodies; 0/Toll-Like Receptor 9; 9007-49-2/DNA; EC C gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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