Objective:To investigate the role of phosphatase and tensin homolog (PTEN) neddylation in the dysregulation of regulatory T cell (Treg) immune function in rheumatoid arthritis (RA) and further explore the pathogenesis of RA.Methods:Peripheral blood samples were collected from 45 healthy volunteers and 45 RA patients in the Yuyao People′s Hospital from Sep. 2021 to Dec. 2022. ELISA was performed to detect the expression levels of the inflammatory factor IFN-γ and Treg-related cytokine IL-10 in serum, and flow cytometry was used to assess the proportion of CD4 +CD25 +FOXP3 + Treg cells. Western Blot analysis was conducted to measure the expression levels of Nedd8-PTEN, ubiquitinated FASN, PTEN, FASN, Neddylation E3 enzyme XIAP, and ubiquitination E3 enzyme TRIM21 in isolated Treg cells. Group comparisons were conducted using an independent samples t-test or the Mann-Whitney U test. Results:Compared with the healthy control group, the expression of IFN-γ was significantly increased [(599± 65) pg/ml vs. (1 066±85) pg/ml, t=-2.06, P<0.001], while IL-10 levels [(601±49) pg/ml vs. (245±41)pg/ml, t=2.05, P<0.001] and the proportion of CD4 +CD25 +FOXP3 + Treg cell [(14.3±0.4)% vs.(6.2±0.6)%, t=19.36, P<0.001] were significantly decreased in the RA patient group (respectively). FASN in Treg cells of RA patients was significantly ubiquitinated, while the PTEN Neddylation level decreased. Additionally, TRIM21 expression was significantly upregulated in RA patients (0.66 ± 0.03 vs. 1.27 ± 0.04, t=-20.85, P<0.001), whereas the expression levels of PTEN (0.858±0.036 vs. 0.377±0.022, t=19.36, P<0.001), XIAP (1.107± 0.065 vs. 0.530±0.015, t=15.03, P<0.001), and FASN protein (1.654±0.031 vs. 0.858±0.025, t=34.64, P<0.001) were significantly downregulated. Conclusion:Decreased levels of PTEN protein Neddylation modification may inhibit the entry of PTEN protein into the nucleus, thereby promoting the ubiquitination degradation of FASN, suppressing fatty acid synthesis in Treg cells, affecting the stability of Treg cell immunosuppressive function, and possibly promoting the progression of RA.

Objective:To investigate the role of phosphatase and tensin homolog (PTEN) neddylation in the dysregulation of regulatory T cell (Treg) immune function in rheumatoid arthritis (RA) and further explore the pathogenesis of RA.Methods:Peripheral blood samples were collected from 45 healthy volunteers and 45 RA patients in the Yuyao People′s Hospital from Sep. 2021 to Dec. 2022. ELISA was performed to detect the expression levels of the inflammatory factor IFN-γ and Treg-related cytokine IL-10 in serum, and flow cytometry was used to assess the proportion of CD4 +CD25 +FOXP3 + Treg cells. Western Blot analysis was conducted to measure the expression levels of Nedd8-PTEN, ubiquitinated FASN, PTEN, FASN, Neddylation E3 enzyme XIAP, and ubiquitination E3 enzyme TRIM21 in isolated Treg cells. Group comparisons were conducted using an independent samples t-test or the Mann-Whitney U test. Results:Compared with the healthy control group, the expression of IFN-γ was significantly increased [(599± 65) pg/ml vs. (1 066±85) pg/ml, t=-2.06, P<0.001], while IL-10 levels [(601±49) pg/ml vs. (245±41)pg/ml, t=2.05, P<0.001] and the proportion of CD4 +CD25 +FOXP3 + Treg cell [(14.3±0.4)% vs.(6.2±0.6)%, t=19.36, P<0.001] were significantly decreased in the RA patient group (respectively). FASN in Treg cells of RA patients was significantly ubiquitinated, while the PTEN Neddylation level decreased. Additionally, TRIM21 expression was significantly upregulated in RA patients (0.66 ± 0.03 vs. 1.27 ± 0.04, t=-20.85, P<0.001), whereas the expression levels of PTEN (0.858±0.036 vs. 0.377±0.022, t=19.36, P<0.001), XIAP (1.107± 0.065 vs. 0.530±0.015, t=15.03, P<0.001), and FASN protein (1.654±0.031 vs. 0.858±0.025, t=34.64, P<0.001) were significantly downregulated. Conclusion:Decreased levels of PTEN protein Neddylation modification may inhibit the entry of PTEN protein into the nucleus, thereby promoting the ubiquitination degradation of FASN, suppressing fatty acid synthesis in Treg cells, affecting the stability of Treg cell immunosuppressive function, and possibly promoting the progression of RA.