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

A Lartigue, P Courville, I Auquit, A François… - The Journal of …, 2006 - journals.aai.org
A Lartigue, P Courville, I Auquit, A François, C Arnoult, F Tron, D Gilbert, P Musette
The Journal of Immunology, 2006journals.aai.org
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 …
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.
journals.aai.org