Th17-related cytokines are expressed in joints of spondyloarthritis as well as RA patients. IL-23 levels, however, correlate with disease activity parameters in RA only. These results point towards a differential regulation of the Th17 cytokine system in spondyloarthritis compared with RA.

BackgroundImmunological and genetic findings implicate Th17 effector cytokines in the pathogenesis of inflammatory bowel disease (IBD). Expression of Th17 pathway-associated genes is mainly studied in colonic disease. The present study assessed the mRNA expression levels of Th17 effector cytokines (IL17A, IL17F, IL21, IL22 and IL26) and genes involved in differentiation (IL6, IL1B, TGFB1, IL23A and STAT3) and recruitment of Th17 cells (CCR6 and CCL20) by quantitative real-time PCR analysis of colonic and ileal biopsies from 22 healthy control subjects, 26 patients with Crohn's disease (CD) and 12 patients with ulcerative colitis (UC). Inflammation was quantified by measuring expression of the inflammatory mediators IL8 and TNF.ResultsEvaluation of mRNA expression levels in colonic and ileal control samples revealed that TNF, TGFB1, STAT3 and CCR6 were expressed at higher levels in the ileum than in the colon. Expression of all the Th17 pathway-associated genes was increased in inflamed colonic samples. The increased expression of these genes was predominantly observed in samples from UC patients and was associated with more intense inflammation. Although increased expression of IL17A, IL17F, IL21 and IL26 was detected in inflamed ileal samples, expression of the indispensable Th17 cell differentiation factors TGFB1 and IL23A, the signaling molecule STAT3 and the Th17 recruitment factors CCR6 and CCL20 were unchanged.ConclusionsOur findings suggest that immune regulation is different in colonic and ileal disease, which might have important consequences for therapeutic intervention.

sE-cadherin contributes to the local proinflammatory environment in the joint by favouring TNF-α production by KLRG1(+) CD4(+) T cells. This pathway seems to be operational in both SpA and RA, but not in crystal-induced arthritis.

Spondyloarthritides, or SpA, form a cluster of chronic inflammatory diseases with the axial skeleton as the most typical disease localisation, although extra-articular manifestations such as intestinal inflammation may frequently occur during the course of the disease. This review summarises recent progress in our understanding of the immunopathogenesis of SpA with special emphasis on the cellular constituents considered to be responsible for the initiation and/or perpetuation of inflammation. There are several arguments favouring a role for haematopoietic cells in the pathophysiology of spondyloarthritis, including HLA-B27-associated dendritic cell disturbances, HLA-B27 misfolding properties and T helper 17 cells. In addition, recent studies have pointed toward a pivotal role for stromal cells. A major challenge, however, remains to determine how recently identified genetic associations such as interleukin-23 receptor polymorphisms may influence cellular targets in spondyloarthritis. IntroductionSpondyloarthritides, or SpA, are a group of chronic inflammatory diseases that affect about 0.5% of the Western population. The most typical disease localisation is the axial skeleton, more specifically the spine and sacroiliac joints. Additionally, enthesitis or peripheral arthritis of the large joints of the lower limbs frequently occurs. Extra-articular manifestations are also a common feature in SpA. They include anterior uveitis, psoriasis and inflammatory bowel disease (IBD).SpA refers to a cluster of disorders that were formerly considered separate disease entities. It comprises ankylosing spondylitis (AS), reactive arthritis (ReA), IBD-associated arthritis and some forms of psoriatic arthritis (PsA). This grouping was based on three important considerations: (a) the different disease phenotypes could consecutively manifest in the same patient, (b) overlaps that make it impossible to distinguish between the different disorders are often seen, and (c) different disorders can affect different members of the same family. Apart from the presence of shared environmental factors, this familial aggregation can be explained for the most part by an important hereditary component in the pathogenesis of the disease. First-degree relatives of SpA patients are 40 times more likely than the general population to develop SpA [1,2]. Features of inflammation in spondyloarthritidesFor many years, an intimate relationship between mucosal and joint inflammation has been established (reviewed in [3]). Pioneering studies by Mielants and Veys [4] demonstrated that about 60% of SpA patients displayed microscopic signs of inflammation in the colon and/or ileum which were unrelated to clinical gastrointestinal symptoms. This illustrates that SpA is a disorder in which many different types of organs may be involved. Extensive studies have been undertaken to characterise the nature of the inflammatory infiltrates in synovial tissue, entheses as well as extra-articular tissues such as colon and/or ileum. Bone marrow inflammation may...

Objective. In vitro spontaneous osteoclastogenesis from peripheral blood mononuclear cells (PBMCs) is increased in diseases with excessive bone loss. The purpose of this study was to reassess the role of T lymphocytes in this process.Methods. Fresh or cryopreserved PBMCs obtained from healthy subjects and from patients with rheumatoid arthritis, psoriatic arthritis, and nonpsoriatic spondylarthritis were cultured at high density and stained for tartrate-resistant acid phosphatase (TRAP). Resorption of mineralized matrix was assessed by a dentin disc assay. CD14؉ monocytes and CD3؉ T cells were selected using magnetically labeled antibodies.Results. Numerous multinucleated, TRAP؉, dentin-resorbing osteoclasts developed spontaneously from fresh PBMCs from healthy individuals. This process was abrogated by T cell depletion and was restored by exogenous macrophage colony-stimulating factor (M-CSF) and RANKL, indicating the important role of T cells in spontaneous osteoclastogenesis in vitro. Using physiologic freezing and thawing as a model for the activation of PBMCs, spontaneous osteoclastogenesis was significantly increased in cryopreserved versus fresh cells. Under these conditions, spontaneous osteoclastogenesis was not dependent on T lymphocytes, since it was not influenced by T cell depletion and persisted in purified CD14؉ cell cultures supplemented with M-CSF and RANKL. In contrast to studies with fresh PBMCs, spontaneous osteoclastogenesis under these conditions did not appear to be clearly different between healthy subjects and patients with arthritis.Conclusion. Spontaneous osteoclastogenesis in vitro is dependent on T lymphocytes or on the direct activation of monocytic cells, depending on the test conditions. This variability warrants better validation of the relevance of this functional test for in vivo osteoclastogenesis.