Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Interferon Regulatory Factor-5 (IRF-5) Is Critical for the Development of Lupus in MRL/lpr Mice.
Nagasawa3, Kohei, Ohta1, Akihide, Suematsu3, Rie, Inoue3, Hisako, Koarada3, Syuichi, Aoki2, Shigehisa, Kondo4, Seiji
Department of Clinical Nursing, Saga University, Saga, Japan
Department of Pathology, Saga University, Saga, Japan
Department of Rheumatology, Saga University, Saga, Japan
National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
Interferon Regulatory Factor-5 (IRF-5) is a transcription factor that mediates intracellular signals activated by engagement of the Toll-like receptors (TLRs). IRF-5 polymorphisms are associated with increased or decreased risk of systemic lupus erythematosus (SLE) in various human populations but the precise role of IRF-5 in SLE development is not understood. We examined the role of IRF-5 in the development of murine lupus.
We crossed gene-targeted IRF-433-deficient (IRF-5-/-) mice to MRL/Mpj-lpr/lpr (MRL/lpr) mice and examined the progeny for survival, glomerulonephritis, autoantibody (autoAb) levels, immune system cell populations, and dendritic cell (DC) functions.
We show that IRF-5-/-MRL/lpr mice survive longer than control IRF-5+/+MRL/lpr mice and display only very mild glomerulonephritis. The glomerular deposition of IgG and C3, and the infiltration of CD4+T cells and macrophages into glomeruli was significantly decreased in IRF-5-/-MRL/lpr mice. Anti-nuclear antibodies, anti-dsDNA antibodies, anti-Sm antibodies, and anti-RNP antibodies were decreased in mouse serum, and numbers of activated CD4+ T cells were reduced in the spleen. Splenic DCs from IRF-5-/-MRL/lpr mice produced lower levels of inflammatory cytokines when treated in vitro with TLR7 or TLR9 ligands or immune complexes. Interferon-a production in response to CpG was also decreased.
Our results show that IRF-5 is a crucial driver of lupus development in mice, and indicate that IRF-5 may be an attractive new target for therapeutic intervention to control disease in SLE patients.
To cite this abstract, please use the following information:
Nagasawa, Kohei, Ohta, Akihide, Suematsu, Rie, Inoue, Hisako, Koarada, Syuichi, Aoki, Shigehisa, et al; Interferon Regulatory Factor-5 (IRF-5) Is Critical for the Development of Lupus in MRL/lpr Mice. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :433