Session Type: Abstract Submissions (ACR)
Psoriasis (Ps) is a common immune-mediated inflammatory skin disease and is a well- recognised extra-articular manifestation of the spondyloathopathies (SpA). Genetic studies implicate IL-23 signalling in the pathogenesis of both Ps and SpA. Spondyloarthritis and psoriasis-like disease develop in an IL-23-dependent fashion in ZAP70-mutant SKG mice, which have deficient T cell receptor signaling. We characterized curdlan (1,3-D β-glucan) induced psoriasis-like inflammation in SKG mice, investigating the role of IL-23, IL-22/IL-17, regulatory T cells (Tregs) and microbiota.
SKG mice, IL-17A-deficient SKG mice, Germ Free SKG mice and Foxp3-DTR SKG mice were injected intraperitoneally with curdlan (1,3-D β-glucan) to induce disease. Anti-mouse IL-22, anti-IL-23 or isotype control antibodies were given i.p one day before curdlan, and weekly until sacrifice. Recombinant IL-23 or PBS was administered intra-dermally into ear skin. Outcomes were measured by clinical and histological scoring; cytokines and by qRT-PCR and in supernatants of cultured tissue explants by ELISA and CBA.
Curdlan induced psoriasis-like inflammation in addition to spondyloarthritis in 100% of SKG mice. SKG skin lesions showed a histological phenotype similar to human Ps with elevated constitutive levels of IL-23a(p19) and increased secretion of both IL-17 and IL-22, 7 days after curdlan. Neutralisation of both IL-23 and IL-22 suppressed development of skin inflammation, in contrast IL-17A-deficient SKG mice were only partially spared. Germ Free (GF) SKG mice failed to develop significant skin inflammation after curdlan, however colonization of GF-SKG mice with a limited microbiota induced mild psoriasis-like inflammation. Tregs modulated the severity of skin inflammation through the suppression of IL-23 secretion. Intradermal injection of IL-23 induced IL-22 mediated, microbiota dependent psoriasis-like inflammation in naïve SKG mice.
In curdlan-treated SKG mice IL-23-driven psoriasis-like inflammation is induced in the setting of spondyloarthritis. The skin inflammation recapitulates several features of human Ps and is dependent on the relative contributions of IL-17, IL-22, microbiota and the balance of Tregs and T effector cells.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-23-mediates-psoriasis-like-inflammation-in-the-skg-mouse-model-of-spondyloarthropathy/