Interleukin-17A Is Produced by CD4+ but Not CD8+ T Cells in Synovial Fluid Following T Cell Receptor Activation and Regulates Different Inflammatory Mediators Compared to Tumor Necrosis Factor in a Model of Psoriatic Arthritis Synovitis

Objective: Interleukin-17A (IL-17A) and tumor necrosis factor (TNF) contribute to the pathogenesis of psoriatic arthritis (PsA). However, their functional relationship in PsA synovitis has not been fully elucidated. Additionally, although CD8+ T cells in PsA have been recognized via flow cytometry as a source of IL-17A production, it is not clear whether CD8+ T cells secrete IL-17A under more physiologically relevant conditions in the context from PsA synovitis. This study was undertaken to clarify the roles of IL-17A and TNF in the synovial fluid (SF) from patients with PsA and investigate the impact of CD8+ T cells on IL-17A production. Methods: IL-17A+ T cells were identified by flow cytometry in SF samples from 20 patients with active PsA, blood samples from 22 treatment-naive patients with PsA, and blood samples from 22 healthy donors. IL-17A+ T cells were sorted from 12 PsA SF samples and stimulated using anti-CD3/anti-CD28 or phorbol myristate acetate (PMA) and ionomycin ex vivo, alone (n = 3) or together with autologous monocytes (n = 3) or PsA fibroblast-like synoviocytes (FLS) (n = 5–6). To evaluate the differential allogeneic effects of neutralizing IL-17A and TNF, SF CD4+ T cells and PsA FLS cocultures were also used (n = 5–6). Results: Flow cytometry analyses of SF samples from patients with PsA showed IL-17A positivity for CD4+ and CD8+ T cells (IL-17A, median 0.71% [interquartile range 0.35–1.50%] in CD4+ cells; median 0.44% [interquartile range 0.17–1.86%] in CD8+ T cells). However, only CD4+ T cells secreted IL-17A after ant

Psoriasis and cardiovascular risk: Immune-mediated crosstalk between metabolic, vascular and autoimmune inflammation

Introduction and background: In the last few years, a substantial body of evidence indicates that cutaneous psoriasis and psoriatic arthritis patients are at higher risk of developing cardiovascular disease. However, underlying mechanism remains not completely understood. In this review we discuss the role of the immune system in the development of atherosclerosis, focusing on available data implicating the role of an enhanced immune-mediated proinflammatory status in psoriasis and psoriatic arthritis diseases. Methods: A systematic search was performed on Pubmed until November 2014, with preference to the sources published within the past 8 years, including epidemiological studies (prospective and retrospective); cross-sectional case–control studies and reviews. Articles were selected according critical associations using the following keywords: arthritis, immune-mediated inflammatory diseases, and psoriasis. These were combined with closely related keywords reflecting cardiovascular diseases: atherogenesis, endothelial dysfunction, intima media thickness, subclinical atherosclerosis, plaque, thrombosis, thrombus, fibrinolysis, coagulation, and reactive oxygen species. Both types of disease selected terms were separately combined with non-traditional (innate and adaptive pro and anti-inflammatory immune molecules and cells) and traditional (metabolic related conditions and molecules) cardiovascular risk factors. Results and conclusions: Psoriasis and psoriatic arthritis diseases illustrate that immune-mediated activated crossroads of inflammation beyond enhanced cardiovascular risk factors are the result of an interplay between different proatherogenic mediators derived from metabolic, vascular and autoimmune joint and skin inflamed target tissue. Consistent with this point of view, psoriasis and psoriatic arthritis diseases offer an invaluable opportunity to reinforce our knowledge about atherosclerotic cardiovascular disease