Objective <p>To investigate the expression of tumor necrosis factor-alpha (TNF-α)-regulated circular RNAs (circRNAs) in T cells from patients with rheumatoid arthritis (RA).</p> Methods <p>Jurkat cells were co-cultured with TNF-α for seven days, after which circRNA expression profiles were analyzed using next-generation sequencing and validated by real-time polymerase chain reaction. Expression levels of TNF-α-regulated circRNAs were then compared between T cells from 51 RA patients and 29 healthy controls. The biological function of specific circRNAs were further examined through RNA pull-down assays and transfection experiments.</p> Results <p>Twenty-one circRNAs were under-expressed in Jurkat cells following chronic TNF-α exposure. Among these, 11 circRNAs were significantly downregulated in T cells from patients with RA. The expression levels of circ-UBX domain protein 7 (UBXN7), circ-Coiled-Coil Domain Containing 134 (CCDC134), and circ-Pyridoxal Dependent Decarboxylase Domain Containing 1 (PDXDC1) were inversely correlated with Disease Activity Score-28 (DAS-28) for RA. Circ-CCDC134 was found to interact with protein phosphatase 2A regulatory subunit A alpha isoform (PPP2R1A), and suppresses PP2A activity. Overexpression of circ-CCDC134 but not its linear counterpart, enhanced phosphorylation of STAT3 and AKT, leading to increased expression of <i>Interleukin 2</i>, and <i>Interferon gamm</i>a (<i>IFN-γ</i>). In addition, increased expression of circ-CCDC134 reversed the suppressive effect of chronic TNF-α-exposure on IFN-γ and IL-2 secretion in activated Jurkat cells.</p> Conclusion <p>Eleven TNF-α-regulated circRNAs were significantly downregulated in RA T cells, with three showing associations with RA disease activity. Circ-CCDC134 binds to and inhibits PP2A, promoting phosphorylation of STAT3 and AKT and enhancing cytokine secretion. These findings suggest that TNF-α-regulated circRNAs contribute to T cell dysfunction in RA.</p>