IL-23 Mediates Psoriasis-like Inflammation in the SKG Mouse Model of Spondyloarthropathy. Helen Benham1, Linda Rehaume1, Athan Baillet1, Zaied Bhuyan1, Jaclyn Bowman1, Dimeng Pang1, Kristine Kikly2, Geoffrey Strutton3, Matthew Brown1 and Ranjeny Thomas1, 1University of Queensland Diamantina Institute, Brisbane, Australia, 2Biotechnology Discovery Research, Eli Lilly and Co, Indianapolis, IN, 3Department of Pathology, Princess Alexandra Hospital, Brisbane, Australia. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are the two most common forms of chronic immune-mediated inflammatory arthritis, and the IL-23 IL-17 axis is thought to have a critical role in both. RA and SpA on the basis of findings from disease-specific animal models as well as human ex vivo studies. This data suggests that IL-23 mediated Th17 and Th22 cells may have common, as well as divergent roles in the pathogenesis of SpA. The psoriasis-like inflammation was shown to be IL-23 dependent and IL-22 mediated. It identifies differing distribution of IL-23-mediated Th17 and Th22 cells in the peripheral blood, joint and skin of patients with SpA; demonstrates that intestinal IL-23 provokes mucosal dysregulation which drives intestinal inflammation and spondyloarthritis; and characterises IL-23 dependent psoriasis-like inflammation in the SKG mouse model of SpA demonstrating the influence of downstream mediators IL-17 and IL-22, microbiota and Tregs on disease pathogenesis.
Spondyloarthritis (SpA) represents a group of immune-mediated inflammatory diseases that exhibit overlapping clinical features, genetic predisposition, and pathogenic mechanisms (1), and affect 0. McGuckin MA, Thomas R. Interleukin-23 mediates the intestinal response to microbial -1,3-glucan and the development of spondyloarthritis pathology in SKG mice. -glucan triggers spondylarthritis and Crohn’s disease-like ileitis in SKG mice. Article: INTERLEUKIN-23 MEDIATES PSORIASIS-LIKE INFLAMMATION IN THE SKG MOUSE MODEL OF SPONDYLOARTHROPATHY.
Psoriatic arthritis (PsA) is a chronic inflammatory joint disorder with heterogeneous clinical features that may include plaque psoriasis, joint inflammation, enthesitis, dactylitis, and abnormal bone turn over. LL37 bound to keratinocyte DNA activates toll-like receptors (TLRs) on the surface of plasmacytoid dendritic cells in the skin; TLRs in turn trigger plasmacytoid dendritic cells to release a number of signaling proteins, including interferon (IFN ) (Lowes et al. Sherlock et al developed a mouse model of PsA and showed that administration of IL23 led to the proliferation of a special T-cell population, resident to the enthesis, that expressed the IL23 receptor (Sherlock et al. Interleukin-23 mediates the intestinal response to microbial beta-1,3-glucan and the development of spondyloarthritis pathology in SKG mice. Both Th17 and Th22 cells are influenced by the cytokine IL-23, which is required for their expansion and maintenance 13. Th17 and Th22 cells in psoriatic arthritis and psoriasis. 37, Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. E: Serum and synovial fluid levels of p40 IL12/23 in spondyloarthropathy patients. 2 DunussiJoannopoulos K, Collins M, et al: IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation – HL, Liang, et al.
The Axis In Spondyloarthritis Pathogenesis: Th17 And Beyond
We found that CIA was markedly suppressed in IL-17/ mice. These genes highlight the involvement of the IL-23 pathway in disease pathogenesis, and indicate overlaps between the pathogenesis of AS, and of inflammatory bowel disease. Lastly, the demonstration that the association of ERAP1 variants with psoriasis in HLA-Cw6-positive, but not Cw6-negative 46, cases, suggests that the mechanism by which HLA-Cw6 is involved in psoriasis is similar to that by which HLA-B27 is involved in AS. As mentioned above, -glucan exposure in skg mice induces spondyloarthritis in a TH17 dependent model; In patients with PsA, CCR6+ and IL-23R + T cells numbers were elevated in SF compared to PB. Introduction Psoriasis (Ps) is a common inflammatory disease of the skin affecting 1 to 3 of the population 1-3. IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. The IL-23-mediated enthesitis is reduced in the presence of IL-17 and IL-22 neutralizing antibodies; however, in contrast to IL-22, IL-17 alone is not sufficient to induce enthesitis 135. At baseline, MRL/lpr mice present a higher frequency of IL-17-producing cells than nonautoimmune mice like B6 strain (unpublished data, 155 ). Psoriasis is completed with arthritis in one-third of the patients during the development of the disease. This new mouse model has several features of Ps and PsA-like disease. Spondyloarthritis is a general term for a group of rheumatic.