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Abstract
This study tested the hypothesis that subsets of human T helper cells can orchestrate leukocyte adhesion to synovial fibroblasts (SFbs), thus regulating the retention of leukocytes in the joints of juvenile idiopathic arthritis (JIA) patients. Several cell types, such as monocytes/macrophages, granulocytes, T and B lymphocytes, SFbs and osteoclasts participate in joint tissue damage JIA. Among T cells, an enrichment of classic and non-classic Th1 subsets, has been found in JIA synovial fluid (SF), compared to peripheral blood (PB). Moreover, it has been shown that IL-12 in the SF of inflamed joints mediates the shift of Th17 lymphocytes towards the non-classic Th1 subset. Culture supernatants of Th17, classic and non-classic Th1 clones, have been tested for their ability to stimulate proliferation, and to induce expression of adhesion molecules on SFbs, obtained from healthy donors. Culture supernatants of both classic and non-classic Th1, but not of Th17, clones, were able to induce CD106 (VCAM-1) up-regulation on SFbs. This effect, mediated by tumor necrosis factor (TNF)-α, was crucial for the adhesion of circulating leukocytes on SFbs. Finally, we found that SFbs derived from SF of JIA patients expressed higher levels of CD106 than those from healthy donors, resembling the phenotype of SFbs activated in vitro with Th1-clones supernatants. On the basis of these findings, we conclude that classic and non-classic Th1 cells induce CD106 expression on SFbs through TNF-α, an effect that could play a role in leukocytes retention in inflamed joints.
Highlights
Inflammatory responses play a key role in host defense from foreign agents but can be responsible of tissue damage, for example in autoimmune diseases
The present study aimed to identify factors which may mediate the interplay between CD4+ T effector cells synovial fibroblasts (SFbs) in terms of synovial activation and involvement of inflammatory cells in immune mediated arthritis
Since T helper lymphocytes orchestrate the inflammation mainly through the production of cytokines that act on resident and inflammatory cells present in the joints, we initially evaluated the ability of Th17, classic and nonclassic Th1 clones-derived supernatants to induce adhesion molecules expression on SFbs isolated from the synovia of healthy subjects
Summary
Inflammatory responses play a key role in host defense from foreign agents but can be responsible of tissue damage, for example in autoimmune diseases. Th17 cells defend the body from extracellular bacterial and fungal infections [4,5,6,7], express the transcription factor RORC [8], the IL-23 receptor (IL-23R), the chemokine receptor CCR6 [9, 10], and the lectin receptor CD161 [11] Beyond their protective role in the clearance of extracellular pathogens, Th lymphocytes have been described to play a role in the pathogenesis of several autoimmune and inflammatory diseases, such as multiple sclerosis, inflammatory bowel disease (IBD), psoriasis, rheumatoid arthritis (RA), and JIA [1, 12], and atopic disorders. Extensive studies in adult RA have shown the existence of SFbs that produce cytokines and matrix-degrading enzymes, playing a crucial role in cartilage destruction and inflammation [19]
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