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Role of TLR9 in Anti-Nucleosome and Anti-DNA Antibody Production in lpr Mutation-Induced Murine Lupus¹

Aurelia Lartigue^*, Philippe Courville^*,, Isabelle Auquit^*, Arnaud François, Christophe Arnoult^*, Francois Tron^*,, Daniele Gilbert^*, and Philippe Musette^2,*,

^* 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, France; and Laboratoire d’Anatomie-Pathologique, Laboratoire d’Immunopathologie Clinique et Expérimentale, and Service de Dermatologie, Centre Hospitalier Universitaire Charles Nicolle, Rouen, France

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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