Interleukin-23 mediates the intestinal response to microbial beta-glucan and the development of spondyloarthritis pathology in SKG mice

Benham, Helen, Rehaume, Linda M., Hasnain, Sumaira Z., Velasco, Jared, Baillet, Athan C., Ruutu, Merja, Kikly, Kristine, Wang, Ran, Tseng, Hsu-Wen, Thomas, Gethin P., Brown, Matthew A., Strutton, Geoffrey, McGuckin, Michael A. and Thomas, Ranjeny (2014) Interleukin-23 mediates the intestinal response to microbial beta-glucan and the development of spondyloarthritis pathology in SKG mice. Arthritis and Rheumatology, 66 7: 1755-1767. doi:10.1002/art.38638

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Author Benham, Helen
Rehaume, Linda M.
Hasnain, Sumaira Z.
Velasco, Jared
Baillet, Athan C.
Ruutu, Merja
Kikly, Kristine
Wang, Ran
Tseng, Hsu-Wen
Thomas, Gethin P.
Brown, Matthew A.
Strutton, Geoffrey
McGuckin, Michael A.
Thomas, Ranjeny
Title Interleukin-23 mediates the intestinal response to microbial beta-glucan and the development of spondyloarthritis pathology in SKG mice
Formatted title
Interleukin-23 mediates the intestinal response to microbial β-1,3-glucan and the development of spondyloarthritis pathology in SKG mice
Journal name Arthritis and Rheumatology   Check publisher's open access policy
ISSN 2326-5191
2326-5205
Publication date 2014-07-01
Year available 2014
Sub-type Article (original research)
DOI 10.1002/art.38638
Volume 66
Issue 7
Start page 1755
End page 1767
Total pages 13
Place of publication Hoboken, NJ, United States
Publisher Jossey Bass
Language eng
Formatted abstract
Objective: Spondyloarthropathies (SpA) occur in 1% of the population, and include ankylosing spondylitis and arthropathy of inflammatory bowel disease (IBD), with characteristic spondylitis, arthritis, enthesitis and IBD. Genetic studies implicate IL-23 receptor signaling in the development of SpA and IBD, and IL-23 over-expression in mice is sufficient for enthesitis, driven by entheseal-resident T cells. However in genetically-prone individuals, it is not clear where IL-23 is produced and how it drives the SpA syndrome, including IBD or sub-clinical gut inflammation of ankylosing spondylitis. Moreover, it is unclear why specific tissue involvement varies between patients with SpA. We determined the location of IL-23 production and its role in SpA pathogenesis in BALB/c ZAP70W163C-mutant (SKG) mice injected i.p. with beta-1,3-glucan (curdlan).

Methods: Eight weeks after curdlan injection of wild type or IL-17-deficient SKG or BALB/c mice, pathology was scored in tissue sections. Mice were treated with anti-IL-23 or anti-IL22. Cytokine production and endoplasmic reticulum stress were determined in affected organs. Results: In curdlan-treated SKG mice arthritis, enthesitis and ileitis were IL-23-dependent. Enthesitis was specifically dependent on IL-17A and IL-22. IL-23 was induced in the ileum, where it amplified endoplasmic reticulum stress, goblet cell dysfunction and pro-inflammatory cytokine production. IL-17A was pathogenic while IL-22 was protective of ileitis. IL-22+CD3- innate-like cells were increased in lamina propria of ileitis-resistant BALB/c mice, which developed ileitis after curdlan and anti-IL-22.

Conclusion: In response to systemic beta-glucan, intestinal IL-23 provokes local mucosal dysregulation and cytokines driving the SpA syndrome, including IL-17/22-dependent enthesitis. Innate IL-22 production promotes ileal tolerance.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Other title: "IL-23 mediates the intestinal response to microbial beta-glucan and the development of spondyloarthritis pathology in SKG mice".

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2015 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 52 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 01 Apr 2014, 03:51:23 EST by Dr Gethin Thomas on behalf of UQ Diamantina Institute