β-glucan triggers spondylarthritis and Crohn's disease–like ileitis in SKG mice
Article first published online: 26 JUN 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 7, pages 2211–2222, July 2012
How to Cite
Ruutu, M., Thomas, G., Steck, R., Degli-Esposti, M. A., Zinkernagel, M. S., Alexander, K., Velasco, J., Strutton, G., Tran, A., Benham, H., Rehaume, L., Wilson, R. J., Kikly, K., Davies, J., Pettit, A. R., Brown, M. A., McGuckin, M. A. and Thomas, R. (2012), β-glucan triggers spondylarthritis and Crohn's disease–like ileitis in SKG mice. Arthritis & Rheumatism, 64: 2211–2222. doi: 10.1002/art.34423
- Issue published online: 26 JUN 2012
- Article first published online: 26 JUN 2012
- Accepted manuscript online: 10 FEB 2012 04:40PM EST
- Manuscript Accepted: 2 FEB 2012
- Manuscript Received: 24 JUN 2011
- National Health and Medical Research Council. Grant Numbers: 351439, 569938
- Senior Fellowship from the Lions Medical Research Foundation
- Research Fellowships from the National Health and Medical Research Council
- Career Development Award from the National Health and Medical Research Council
- Arthritis Queensland
- Future Fellowship from the Australian Research Council
The spondylarthritides (SpA), including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, and arthritis associated with inflammatory bowel disease, cause chronic inflammation of the large peripheral and axial joints, eyes, skin, ileum, and colon. Genetic studies reveal common candidate genes for AS, PsA, and Crohn's disease, including IL23R, IL12B, STAT3, and CARD9, all of which are associated with interleukin-23 (IL-23) signaling downstream of the dectin 1 β-glucan receptor. In autoimmune-prone SKG mice with mutated ZAP-70, which attenuates T cell receptor signaling and increases the autoreactivity of T cells in the peripheral repertoire, IL-17–dependent inflammatory arthritis developed after dectin 1–mediated fungal infection. This study was undertaken to determine whether SKG mice injected with 1,3-β-glucan (curdlan) develop evidence of SpA, and the relationship of innate and adaptive autoimmunity to this process.
SKG mice and control BALB/c mice were injected once with curdlan or mannan. Arthritis was scored weekly, and organs were assessed for pathologic features. Anti–IL-23 monoclonal antibodies were injected into curdlan-treated SKG mice. CD4+ T cells were transferred from curdlan-treated mice to SCID mice, and sera were analyzed for autoantibodies.
After systemic injection of curdlan, SKG mice developed enthesitis, wrist, ankle, and sacroiliac joint arthritis, dactylitis, plantar fasciitis, vertebral inflammation, ileitis resembling Crohn's disease, and unilateral uveitis. Mannan triggered spondylitis and arthritis. Arthritis and spondylitis were T cell– and IL-23–dependent and were transferable to SCID recipients with CD4+ T cells. SpA was associated with collagen- and proteoglycan-specific autoantibodies.
Our findings indicate that the SKG ZAP-70W163C mutation predisposes BALB/c mice to SpA, resulting from innate and adaptive autoimmunity, after systemic β-glucan or mannan exposure.