gms | German Medical Science

Background: Spondyloarthritis is a family of inflammatory rheumatic diseases that variably affect the joints, spine, skin and intestine. Multiple lines of evidence support a critical role for the IL-23/IL-17A axis, however, many aspects of spondyloarthritis pathogenesis remain poorly understood. Overexpression of IL-23 in adult mice by means of hydrodynamic tail vein injection of IL-23 minicircles results in a spondyloarthritis-like disease. We analyzed factors impacting the disease phenotype in this mouse model.

Methods: We hydrodynamically injected male and female B10.RIII mice and male C57BL/6 mice at 8-12 weeks of age with 0.5 μg of IL-23 minicircles (System Biosciences, EEV651A-1). Control mice received no minicircles. To study the role of intestinal microbiota, mice were treated with antibiotics (vancomycin or gentamicin) in the drinking water starting two weeks prior to disease induction. We monitored clinical arthritis scores, paw swelling, and body weight. Animals were euthanized after two weeks. Serum IL-23 levels were measured by ELISA. Skin, joints and colon were harvested for histology and gene expression analysis by qPCR.

Results: Male B10.RIII mice, but not C57BL/6 mice, developed arthritis within 4-8 days after minicircle injection. Serum IL-23 levels were comparable between strains. Both B10.RIII and C57BL/6 mice lost ~15% of body weight over two weeks and developed colitis. Consistent with the clinical phenotype, B10.RIII injected with IL-23 minicircles had increased expression of IL-17A, IL-22, TNF and IL-1β in arthritic joints, whereas minicircle-injected C57BL/6 mice did not differ from un-injected controls. Female B10.RIII mice developed more severe arthritis than male mice. Colitis severity was similar but female B10.RIII mice did not loose weight. Treatment of B10.RIII mice with Gentamicin suppressed the development of clinical arthritis without impact on weight loss or colitis.

Conclusion: IL-23 minicircle-induced disease in our lab is characterized by destructive arthritis, psoriasis-like skin disease and colitis. We find that sex and genetic background of the animals affect the disease phenotype. Intestinal microbiota also appear to play a critical role. Even though the absence of arthritis in C57BL/6 mice poses a challenge, hydrodynamic injection of IL-23 minicircles in mice is a useful tool to study spondyloarthritis disease mechanisms.