Scientists have discovered a group of immune cells that cause joint inflammation in rheumatoid arthritis (RA) by secreting a factor called interleukin (IL)-21 — a potential new target for RA therapeutics.
The study “Synovial IL-21/TNF-producing CD4+ T cells induce joint destruction in rheumatoid arthritis by inducing matrix metalloproteinase production by fibroblast-like synoviocytes,” appeared in the Journal of Leukocyte Biology.
Maria Cristina Lebre, PhD, the study’s first author and a researcher at the University of Amsterdam in the Netherlands, noted that RA patients with inflamed joins have difficulty walking and using their hands.
“New targeted therapies such as that proposed in this study (decrease in inflammation) will certainly improve the quality of life of patients by increasing their mobility,” Lebre said in a press release.
A group of cells of the immune system, called T-cells, has been shown to play a key role in bone and cartilage destruction in RA. These cells are defined by subgroups, according to their production and release of different mediators (cytokines). One of these cytokines is IL-21, and the cells producing it are called IL-21–producing T-cells.
The role of these cells in RA, however, has remained unknown until this latest Dutch study. The team isolated T-cells from synovial fluid (fluid in the cavities of synovial joints) from patients with RA that produced IL-21 and another cytokine called tumor necrosis factor (TNF). They also isolated T-cells that do not produce these cytokines and compared both cell types.
Specifically, the team incubated in vitro cells producing IL-21 with synovial fibroblasts — the main contributors to joint inflammation in RA — and did the same thing with cells that do not produce Il-21 and TNF (control cells). The IL-21–producing T-cells induced the synovial fibroblasts to produce and secrete pro-inflammatory cytokines; this did not happen with control cells.
These results suggest that IL-21- and TNF-producing cells T-cells promote synovial inflammation/joint destruction in patients with RA. Notably, it also suggests that therapeutics blocking IL-21, combined with anti-TNF drugs, may be an effective therapy for RA patients, particularly for RA patients who fail to respond to other therapeutics.
“Patients with rheumatoid arthritis often become refractory to treatment, provoking the need to try different drugs targeting different pathways,” said John Wherry, PhD, deputy editor of the Journal of Leukocyte Biology. “The identification of a new inflammatory target in rheumatoid arthritis holds promise for better treatment for these patients and perhaps those with other autoimmune or inflammatory diseases.”