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The Expression of P2X7 Receptor on Th1, Th17, and Regulatory T Cells in Patients with Systemic Lupus Erythematosus or Rheumatoid Arthritis and Its Correlations with Active Disease
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-08-31 , DOI: 10.4049/jimmunol.2000222
Mingxuan Li 1 , Chuanyu Yang 2 , Yunhai Wang 3 , Wei Song 1 , Lina Jia 1 , Xiaoxiang Peng 4 , Ronglan Zhao 4
Affiliation  

Key Points P2X7R expression on Th subsets is changed in RA and SLE patients. Th17 cell P2X7R expression is positively related to DAS28 and SLEDAI scores. Highly expressed P2X7R on CD4+ PBMCs is functional in RA and SLE patients. P2X7 receptor (P2X7R) is highly expressed on immune cells, triggering the release of cytokines and regulating autoimmune responses. To investigate P2X7R surface expression on T helper (Th) 1, Th17, and regulatory T (Treg) cells in patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) and correlations with disease activity, 29 SLE and 29 RA patients and 18 healthy controls (HCs) were enrolled. We showed that SLE and RA patients had significantly higher levels of plasma cytokines (IFN-γ, IL-1β, IL-6, IL-17A, and IL-23), frequencies of Th1 and Th17 cells, and expression of P2X7R on Th1 and Th17 than HCs, and the Th17/Treg ratio was significantly increased, whereas Treg cell levels were significantly decreased. The Ca2+ influx increase following BzATP stimulation was significantly higher in CD4+PBMCs from SLE and RA patients than in HCs. Blood levels of shed P2X7R were increased in SLE and RA patients. Furthermore, 28-joint Disease Activity Score and SLE Disease Activity Index score showed negative correlations with Treg cell levels and positive correlations with Th17/Treg ratio and Th17 cell P2X7R expression. Interestingly, Th17 cell P2X7R expression was closely correlated with IL-1β, C-reactive protein, the erythrocyte sedimentation rate, anticyclic citrullinated peptide Abs, albumin, and C4. These data indicate that increased Th17 cell P2X7R expression is functionally and positively related to disease activity and some inflammatory mediators in SLE and RA patients, and P2X7R could be critical in promoting the Th17 immune response and contributing to the complex pathogenesis of SLE and RA.

中文翻译:

P2X7受体在系统性红斑狼疮或类风湿关节炎患者Th1、Th17和调节性T细胞上的表达及其与活动性疾病的相关性

关键点 RA 和 SLE 患者中 Th 亚群上的 P2X7R 表达发生了变化。Th17 细胞 P2X7R 表达与 DAS28 和 SLEDAI 评分呈正相关。CD4+ PBMC 上高表达的 P2X7R 在 RA 和 SLE 患者中起作用。P2X7 受体 (P2X7R) 在免疫细胞上高度表达,触发细胞因子的释放并调节自身免疫反应。为了研究系统性红斑狼疮 (SLE) 或类风湿性关节炎 (RA) 患者中 T 辅助 (Th) 1、Th17 和调节性 T (Treg) 细胞的 P2X7R 表面表达及其与疾病活动性的相关性,29 名 SLE 和 29 名 RA 患者和招募了 18 名健康对照 (HC)。我们发现 SLE 和 RA 患者的血浆细胞因子水平(IFN-γ、IL-1β、IL-6、IL-17A 和 IL-23)、Th1 和 Th17 细胞的频率、P2X7R 在 Th1 和 Th17 上的表达高于 HC,Th17/Treg 比值显着增加,而 Treg 细胞水平显着降低。在 SLE 和 RA 患者的 CD4+PBMC 中,BzATP 刺激后 Ca2+ 流入增加显着高于 HC。SLE 和 RA 患者血液中脱落的 P2X7R 水平升高。此外,28 关节疾病活动评分和 SLE 疾病活动指数评分与 Treg 细胞水平呈负相关,与 Th17/Treg 比率和 Th17 细胞 P2X7R 表达呈正相关。有趣的是,Th17 细胞 P2X7R 表达与 IL-1β、C 反应蛋白、红细胞沉降率、抗环瓜氨酸肽抗体、白蛋白和 C4 密切相关。
更新日期:2020-08-31
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