title: CXCR3/CXCL10 expression in the synovium of children with juvenile idiopathic arthritis.
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. IFNgamma-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.
authors.affiliation: Department of Paediatrics, Padua University School of Medicine, Italy. martini@pediatria.unipd.it
authors.forename: Georgia
authors.initials: G
authors.lastname: Martini
authors.forename: Francesco
authors.initials: F
authors.lastname: Zulian
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Marta
authors.initials: M
authors.lastname: Bortoli
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.forename: Anna
authors.initials: A
authors.lastname: Cabrelle
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Valente
authors.forename: Franco
authors.initials: F
authors.lastname: Zacchello
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostini
mesh_terms: D000293:Adolescent; D000328:Adult; D001171:Arthritis, Juvenile / Q000235:genetics / Q000378:metabolism*; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000096:biosynthesis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000166:cytology; D013583:Synovial Membrane / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine
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