Abstract
The accumulation of T cells in the synovial membrane is the crucial step in the pathophysiology of the inflammatory processes characterizing juvenile idiopathic arthritis (JIA). In this study, we evaluated the expression and the pathogenetic role in oligoarticular JIA of a CXC chemokine involved in the directional migration of activated T cells, i.e. IFNγ-inducible protein 10 (CXCL10) and its receptor, CXCR3. Immunochemistry with an antihuman CXCL10 showed that synovial macrophages, epithelial cells, and endothelial cells bear the chemokine. By flow cytometry and immunochemistry, it has been shown that CXCR3 is expressed at high density by virtually all T lymphocytes isolated from synovial fluid (SF) and infiltrating the synovial membrane. Particularly strongly stained CXCR3+ T cells can be observed close to the luminal space and in the perivascular area. Furthermore, densitometric analysis has revealed that the mRNA levels for CXCR3 are significantly higher in JIA patients than in controls. T cells purified from SF exhibit a definite migratory capability in response to CXCL10. Furthermore, SF exerts significant chemotactic activity on the CXCR3+ T-cell line, and this activity is inhibited by the addition of an anti-CXCL10 neutralizing antibody. Taken together, these data suggest that CXCR3/CXCL10 interactions are involved in the pathophysiology of JIA-associated inflammatory processes, regulating both the activation of T cells and their recruitment into the inflamed synovium.
Highlights
The trafficking and accumulation of immunocompetent cells are essential components in the pathophysiology of the inflammatory processes
In order to verify whether macrophages express CXCL10 morphology, data were confirmed by the use of confocal microscopy
Our principal findings are that in juvenile idiopathic arthritis (JIA), CXCL10/IP-10 is strongly expressed in synovial membranes and is released into synovial fluid (SF), where it exerts a definite chemotactic activity on CXCR3+ T-cell clones and on T cells purified from SF; and that there
Summary
The trafficking and accumulation of immunocompetent cells are essential components in the pathophysiology of the inflammatory processes. A number of recent data suggest that most of these events are regulated by chemokines, a superfamily of 8–10 kDa molecules that has been divided into four branches (C, CC, CXC, and CXXXC) according to variations in a shared cysteine [1,2]. Structural variations of chemokines have been associated with differences in their ability to regulate the trafficking of immune cells during inflammatory disorders. The biological activity of chemokines is mediated by seven-transmembrane-domain, G-protein-coupled receptors classified as. Chemokine receptors are constitutively expressed on some cells, whereas they are inducible on others [3]
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