Related Experiment Video
Updated: Apr 19, 2026
Preliminary Study on Acupuncture Combined with Grain-sized Moxibustion for Treating Rheumatoid Arthritis with Finger Joint Pain
Published on: May 16, 2025
Targeting the Fas/FasL system in Rheumatoid Arthritis therapy: Promising or risky?
Flavia Calmon-Hamaty1, Rachel Audo1, Bernard Combe2
1Institut de Génétique Moléculaire de Montpellier, Université Montpellier Sud de France, 1919 route de Mende, CNRS, UMR5535, Montpellier, France.
Abstract:
Rheumatoid Arthritis (RA) is a chronic inflammatory disease affecting synovial joints. Tumor necrosis factor (TNF) α is a key component of RA pathogenesis and blocking this cytokine is the most common strategy to treat the disease. Though TNFα blockers are very efficient, one third of the RA patients are unresponsive or present side effects. Therefore, the development of novel therapeutic approaches is required. RA pathogenesis is characterized by the hyperplasia of the synovium, closely associated to the pseudo-tumoral expansion of fibroblast-like synoviocytes (FLS), which invade and destroy the joint structure. Hence, depletion of RA FLS has been proposed as an alternative therapeutic strategy. The TNF family member Fas ligand (FasL) was reported to trigger apoptosis in FLS of arthritic joints by binding to its receptor Fas and therefore suggested as a promising candidate for targeting the hyperplastic synovial tissue. However, this cytokine is pleiotropic and recent data from the literature indicate that Fas activation might have a disease-promoting role in RA by promoting cell proliferation. Therefore, a FasL-based therapy for RA requires careful evaluation before being applied. In this review we aim to overview what is known about the apoptotic and non-apoptotic effects of Fas/FasL system and discuss its relevance in RA.
Insights
Rheumatoid arthritis (RA) treatments targeting tumor necrosis factor alpha (TNFα) are common but not always effective. The Fas/FasL system
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Rheumatoid arthritis (RA) is a chronic inflammatory joint disease.
- Tumor necrosis factor alpha (TNFα) blockers are a common RA treatment, but many patients are unresponsive or experience side effects.
- Fibroblast-like synoviocytes (FLS) contribute to RA joint destruction, making their depletion a potential therapeutic strategy.
Purpose of the Study:
- To review the dual role of the Fas/FasL system in RA.
- To evaluate Fas ligand (FasL) as a potential therapeutic agent for RA by examining its apoptotic and non-apoptotic effects on fibroblast-like synoviocytes (FLS).
Main Methods:
- Literature review of studies on the Fas/FasL system in Rheumatoid Arthritis.
- Analysis of research on the apoptotic and non-apoptotic effects of Fas activation in fibroblast-like synoviocytes (FLS).
Main Results:
- The Fas/FasL system has a complex role in RA pathogenesis.
- FasL can induce apoptosis in FLS, suggesting a therapeutic benefit.
- However, Fas activation may also promote RA by increasing cell proliferation, indicating potential risks.
Conclusions:
- The Fas/FasL system presents a potential therapeutic target for RA, but its dual role requires careful consideration.
- Further research is needed to fully understand and safely harness the Fas/FasL pathway for RA treatment.
- Targeting FLS via FasL warrants cautious evaluation due to potential disease-promoting effects.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF