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.
Conclusion: Our data indicate an important role of FucT-VII in the enhanced homing of T cells to the inflamed synovium.