AB0056 TNFR2 PROMOTES INFLAMMATORY PROGRAMS IN FIBROBLAST-LIKE SYNOVIOCYTES

Background: TNF-mediated fibroblast-like synoviocyte (FLS) activation is important for inflammation and joint destruction in rheumatoid arthritis (RA). The role of TNF-receptor 1 (TNFR1) FLS has thoroughly been characterized. functions TNFR2 are, however, largely unknown. Objectives: To investigate the contribution to FLS. Methods: RA-FLS were transfected with TNFR2-targeting siRNA pools transcriptional changes determined by RNA-seq. QPCR, ELISA immunoblotting used confirm RNA-seq results gain insights into pathways that regulate TNFR2-mediated Results: TNF stimulation resulted a strong upregulation proinflammatory cytokines, chemokines, tissue-degrading enzymes other genes are associated synovial RA. Silencing markedly diminished TNF-response RA-FLS. Especially, “interferon”-stimulated-genes (ISGs) including putative master regulators inflammation, such as CXCR3 chemokines CXCL9, CXCL10 CXCL11 affected knockdown TNFR2. Consistently, immunoblots showed was required TNF-induced phosphorylation transcription factor STAT1, which known mediate ISGs, chemokines. Conclusion: regulates gene expression via STAT1 thereby contributes detrimental effects inflammation. Disclosure Interests: None declared