CXCR3/CXCL10 expression in the synovium of children with juvenile idiopathic arthritis.
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.
Martini
Georgia
G
Department of Paediatrics, Padua University School of Medicine, Italy. martini@pediatria.unipd.it
Zulian
Francesco
F
Calabrese
Fiorella
F
Bortoli
Marta
M
Facco
Monica
M
Cabrelle
Anna
A
Valente
Marialuisa
M
Zacchello
Franco
F
Agostini
Carlo
C
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
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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