Role of phosphatase and tensin homolog neddylation-mediated regulation of regulatory T cell immune function in the progression of rheumatoid arthritis
10.3760/cma.j.cn141217-20240318-00089-1
- VernacularTitle:磷酸酯酶与张力蛋白同源物类泛素化修饰介导调节性T细胞免疫功能在类风湿关节炎进展中的作用探讨
- Author:
Mengda SHEN
1
;
Cong WEI
;
Wei ZOU
;
Yingjun ZHU
;
Wei WEI
Author Information
1. 宁波大学附属阳明医院（余姚市人民医院）风湿免疫科，宁波 315400
- Publication Type:Journal Article
- Keywords:
Arthritis, rheumatoid;
T cells, regulatory;
Neddylation;
Phosphatase and tensin homolog;
Fatty acid synthase
- From:
Chinese Journal of Rheumatology
2025;29(9):759-763
- CountryChina
- Language:Chinese
-
Abstract:
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.
