Rheumatoid arthritis synovial fibroblasts produce a soluble form of the interleukin-7 receptor in response to pro-inflammatory cytokines.
Bottom Line: Activated CD4 T cells also produce sIL-7R. sIL-7R serum levels are higher in RA patients as compared to controls.In DMARD-resistant patients, high sIL-7R serum concentrations are strongly associated with poor response to TNF-blockade.In conclusion, sIL-7R is induced by pro-inflammatory cytokines in RA FLS. sIL-7R could qualify as a new biomarker of response to therapy in RA.
Affiliation: Rheumatology Department, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.Show MeSH
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Mentions: Because sIL-7R transcripts result from an alternative splicing of IL-7R mRNAs, we wondered whether expression of both IL-7R isoforms is similarly regulated in FLS by the addition of pro-inflammatory cytokines known to play a role in the pathogenesis of RA. We found that mRNA levels of both the membrane-bound and soluble forms of IL-7R are up-regulated by the addition of TNF-α, IL-1β and combinations of TNF-α and IL-1β or TNF-α and IL-17 (Fig. 2A). Flow cytometry experiments were, however, unable to detect any cell surface expression of the membrane-bound IL-7R on FLS under any of these conditions (Fig. 2B). By contrast, ELISA experiments performed on culture supernatants indicated that sIL-7R secretion is induced in FLS by TNF-α, IL-1β and the combination of both cytokines (Fig. 2C). Interestingly, sIL-7R gene expression is negative in activated CD8 T and B cells but slightly positive in activated CD4 T cells (Fig. 1A). Taken together, these results indicate that sIL-7R is a marker of fibroblast and, to a lesser extent, CD4 T-cell activation.
Affiliation: Rheumatology Department, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.