Knockdown of PELI1 promotes Th2 and Treg cell differentiation in juvenile idiopathic arthritis

Abstract

Pellino1 (PELI1) is a key regulator of inflammatory and autoimmune diseases. The role of PELI1 in juvenile idiopathic arthritis (JIA) is unclear. The correlation between serum PELI1 mRNA levels and clinical indicators of JIA patients was evaluated by Pearson correlation analysis. The percentage of Th1, Th2, Th17 and Treg cells was analyzed by flow cytometry. ELISA kits were used to detect cytokine levels in serum and cell supernatants. Co-immunoprecipitation experiments were performed to validate PELI1 and TCF-1 interactions. The protein and ubiquitination levels of TCF-1 were detected by western blot. The results showed that JIA patients have high serum PELI1 levels. PELI1 levels were positively correlated with erythrocyte sedimentation rate, C-reactive protein levels and JADAS27 scores in JIA patients. Interfering with PELI1 promoted naïve CD4⁺ T cell differentiation to Th2 and Treg cells and increased IL-4 and IL-10 levels, while inhibiting their differentiation to Th1 and Th17 cells and decreasing IFN-γ and IL-17 levels. PELI1 increased TCF-1 ubiquitination levels and accelerated its degradation. Inhibition of TCF-1 reduced the effects of interfering with PELI1 on cell differentiation and cytokine levels. In conclusion, Silencing of PELI1 facilitated the naïve CD4⁺ T cell differentiation into Th2 and Treg cells by TCF-1.