Incidence and Severity of Spondyloarthritis and Ileitis Are Determined by Interaction Between the Microbiota and Genetic Susceptibility in Beta-Glucan-Treated Skg Mice

Rehaume, L., Mondot, S., Aguirre de Cárcer, D., Velasco, J., Benham, H., Hasnain, S., Ruutu, M., McGuckin, M. and Morrison, M. (2013). Incidence and Severity of Spondyloarthritis and Ileitis Are Determined by Interaction Between the Microbiota and Genetic Susceptibility in Beta-Glucan-Treated Skg Mice. In: Special Issue: Australian Rheumatology Association in conjunction with the Rheumatology Health Professionals Association 54th Annual Scientific Meeting: Conference Abstracts. 54th Annual Scientific Meeting of the Australian Rheumatology Association in conjunction with the Rheumatology Health Professionals Association, Perth, WA Australia, (6-6). 18 -22 May 2013. doi:10.1111/imj.12139


Author Rehaume, L.
Mondot, S.
Aguirre de Cárcer, D.
Velasco, J.
Benham, H.
Hasnain, S.
Ruutu, M.
McGuckin, M.
Morrison, M.
Title of paper Incidence and Severity of Spondyloarthritis and Ileitis Are Determined by Interaction Between the Microbiota and Genetic Susceptibility in Beta-Glucan-Treated Skg Mice
Conference name 54th Annual Scientific Meeting of the Australian Rheumatology Association in conjunction with the Rheumatology Health Professionals Association
Conference location Perth, WA Australia
Conference dates 18 -22 May 2013
Proceedings title Special Issue: Australian Rheumatology Association in conjunction with the Rheumatology Health Professionals Association 54th Annual Scientific Meeting: Conference Abstracts   Check publisher's open access policy
Journal name Internal Medicine Journal   Check publisher's open access policy
Place of Publication Richmond, VIC Australia
Publisher Wiley-Blackwell Publishing Asia
Publication Year 2013
Year available 2013
Sub-type Published abstract
DOI 10.1111/imj.12139
Open Access Status
ISSN 1444-0903
1445-5994
Volume 43
Issue S2
Start page 6
End page 6
Total pages 1
Language eng
Formatted Abstract/Summary
Aim: Spondyloarthritis and inflammatory bowel disease (IBD) share genetic associations and coincide in many patients. Rodent models typically improve in germ-free (GF) conditions and intestinal microbial diversity is reduced in Crohn's disease, implicating the microbiota in pathogenesis. We hypothesized that microbiota contribute to spondyloarthritis and ileitis in SKG mice, where the ZAP-70(W163C) mutation reduces T cell receptor signaling.

Methods: SKG and BALB/c mice were housed in SPF or rederived to GF conditions then injected i.p. with 1,3-D beta-glucan (curdlan). Joint, tail and small intestinal histological sections were scored at sacrifice. The fecal microbiota was assessed by 454 pyrosequencing. Cytokine and endoplasmic reticulum (ER) stress marker transcription were measured by qRT-PCR.

Results: Under SPF conditions, curdlan-treated SKG developed severe IL-23- and TLR4-dependent spondyloarthritis and Crohn's-like ileitis. BALB/c control mice developed mild peripheral arthritis without ileitis. Under GF conditions, SKG mice had reduced spondyloarthritis incidence and no ileitis. Bacterial reconstitution of GF mice restored spondyloarthritis and ileitis. Within days after curdlan, under SPF but not GF conditions, IL-23 and GRP-78 expression increased in the ileum, positively correlating with mesenteric lymph node Th17 responses. SKG and BALB/c mice co-housed after weaning, then injected with curdlan at 6 weeks of age, developed arthritis with similar disease severity to non-co-housed control mice, but BALB/c mice now developed ileitis. Microbiota profiling demonstrates both ZAP70 genotype and curdlan determine bacterial community structure in co-housed mice. Dysbiosis was associated with intestinal ER stress, reduced mucus-producing cells and increased NF-kB signaling through pathogen or damage-associated molecules in draining lymph node.

Conclusions: The ZAP-70(W163C) predisposes to intestinal dysbiosis triggered by systemic delivery of curdlan, which enhances susceptibility to TLR4-mediated inflammatory signals driving spondyloarthritis.
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Conference Paper
Collection: UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Google Scholar Search Google Scholar
Created: Sun, 09 Jun 2013, 00:40:44 EST by System User on behalf of UQ Diamantina Institute