β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
University of Queensland and Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Merja
M
Ruutu
Gethin
G
Thomas
Roland
R
Steck
Mariapia A
MA
Degli-Esposti
Martin S
MS
Zinkernagel
Kylie
K
Alexander
Jared
J
Velasco
Geoffrey
G
Strutton
Ai
A
Tran
Helen
H
Benham
Linda
L
Rehaume
Robert J
RJ
Wilson
Kristine
K
Kikly
Julian
J
Davies
Allison R
AR
Pettit
Matthew A
MA
Brown
Michael A
MA
McGuckin
Ranjeny
R
Thomas
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity / Q000276:immunology; D007079:Ileitis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000276:immunology; D007596:Joints / Q000276:immunology / Q000473:pathology; D051379:Mice; D025241:Spondylarthritis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D047071:beta-Glucans
D001323:Autoantibodies; D020381:Interleukin-17; D047071:beta-Glucans; C038459:curdlan