Increased expression of alpha(1,3)-fucosyltransferase-VII and P-selectin binding of synovial fluid T cells in juvenile idiopathic arthritis.
OBJECTIVE
The mechanisms controlling the recruitment of T helper type 1 (Th1) cells to the inflamed synovium are not fully understood. Here, we focus on alpha(1,3)-fucosyltransferase-VII (FucT-VII), an enzyme responsible for the generation of functional P- and E-selectin ligands that is upregulated in Th1 cells.


METHODS
Expression of transcripts encoding FucT-VII, interferon-gamma (IFN-gamma), and interleukin 12Rbeta2 (IL-12Rbeta2) were analyzed in T cells purified from synovial fluid (SF) and from peripheral blood (PB) of children with juvenile idiopathic arthritis (JIA) using kinetic reverse transcriptase polymerase chain reaction analysis. Binding of SF and PB T cells to P-selectin was determined by flow cytometry using a soluble P-selectin/IgG1 fusion molecule. Recruitment of T cells to synovial tissue in vivo was studied by analyzing the migration of FucT-VII transfected Jurkat T cells into human rheumatoid synovial tissue grafted into SCID mice.


RESULTS
In patients with JIA, the mRNA levels of FucT-VII, as well as of IFN-gamma and IL-12Rbeta2, were up-regulated in SF T cells compared to paired PB T cells. A higher expression of FucT-VII mRNA in SF T cells was associated with increased binding of T cells to P-selectin. Moreover, FucT-VII expression and increased P-selectin binding capacity of T cells were associated with a polyarticular course of oligoarticular JIA. Expression of FucT-VII in Jurkat T cells resulted in an increased accumulation of these cells in human rheumatoid synovial tissue grafted into SCID mice.


CONCLUSIONS
Our data indicate an important role of FucT-VII in the enhanced homing of T cells to the inflamed synovium.
De Benedetti
Fabrizio
F
Pediatria Generale e Reumatologia, Dipartimento di Pediatria, IRCCS Policlinico San Matteo, Pavia, Italy.
Pignatti
Patrizia
P
Biffi
Mauro
M
Bono
Elisa
E
Wahid
Smaira
S
Ingegnoli
Francesca
F
Chang
Sheng-Yung P
SY
Alexander
Heather
H
Massa
Margherita
M
Pistorio
Angela
A
Martini
Alberto
A
Pitzalis
Costantino
C
Sinigaglia
Francesco
F
Rogge
Lars
L
D000293:Adolescent; D000328:Adult; D000818:Animals; D001171:Arthritis, Juvenile / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D051379:Mice; D016513:Mice, SCID; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053707:Receptors, Interleukin-12; D013582:Synovial Fluid / Q000166:cytology / Q000201:enzymology; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D013601:T-Lymphocytes / Q000201:enzymology* / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation
D019007:P-Selectin; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D007371:Interferon-gamma; D005647:Fucosyltransferases