B cells from Patients with Rheumatoid Arthritis Show Conserved CD39-Mediated Regulatory Function and increased CD39 Expression After Positive Response to Therapy.
B cells from Patients with Rheumatoid Arthritis Show Conserved CD39-Mediated Regulatory Function and increased CD39 Expression After Positive Response to Therapy.
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来自类风湿关节炎患者的B细胞表现出保守的CD39介导的调节功能，在对治疗阳性后的CD39表达增加。
DOI：
10.1016/j.jmb.2020.10.021
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发表时间：
2021-01-08
影响因子：
5.6
通讯作者：
Gruppi, A.
中科院分区：
文献类型：
--
作者：
Zacca, E. R.;Amezcua Vesely, M. C.;Ferrero, P., V;Acosta, C. D., V;Ponce, N. E.;Bossio, S. N.;Mussano, E.;Onetti, L.;Cadile, I;Acosta Rodriguez, E., V;Montes, C. L.;Gruppi, A.
类风湿性关节炎（RA）是一种慢性炎症性疾病，其特征是进行性关节破坏与促炎介质增加相关。在炎症微环境中，外源性ATP （eATP）通过外核苷酶CD39和CD73的连续作用被水解成腺苷，发挥免疫抑制作用。成熟的B细胞组成性地表达这两种外核苷酸酶，将这些细胞转化为潜在的抑制因子。在这里，我们评估了治疗或未治疗RA患者B细胞中CD39和CD73的表达。与健康对照组相比，未经治疗或治疗的RA患者的CD73+CD39+和CD73−CD39+ B细胞亚群的频率以及B细胞上CD73和CD39的表达水平均未出现显著变化（HC）。HC或未经治疗的RA患者CpG+ il -2刺激的B细胞CD39表达增加，抑制CD4+和CD8+ T细胞增殖和细胞内tnf生成。CD39抑制剂可显著恢复HC和未经治疗的RA患者CD4+ T细胞的增殖和tnf生成能力，而CD8+ T细胞则没有，表明未经治疗的RA患者的B细胞保留了CD39介导的调节功能。对治疗有良好反应的患者（R-RA）在治疗后B细胞CD39表达增加，但CD73表达不增加，而大多数无反应（NR）患者的外酶表达减少。B细胞CD39表达的阳性变化与疾病活动度和类风湿因子水平呈负相关。我们的研究结果表明，调节外酶/ADO通路是改善RA病程的潜在治疗靶点。类风湿关节炎（RA）患者的B细胞CD39和CD73表达与健康对照（HC）相似。在对治疗产生积极反应后，B细胞表现出CD39的表达增加，但CD73的表达没有增加，从而提高了水解eATP和抑制CD4+ T细胞增殖和TNF产生的能力。
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction associated with increased pro-inflammatory mediators. In inflammatory microenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exerts immunosuppressive effects, by the consecutive action of the ectonucleotidases CD39 and CD73. Mature B cells constitutively express both ectonucleotidases, converting these cells to potential suppressors. Here, we assessed CD39 and CD73 expression on B cells from treated or untreated patients with RA. Neither the frequency of CD73+CD39+ and CD73−CD39+ B cell subsets nor the levels of CD73 and CD39 expression on B cells from untreated or treated RA patients showed significant changes in comparison to healthy controls (HC). CpG+IL-2-stimulated B cells from HC or untreated RA patients increased their CD39 expression, and suppressed CD4+ and CD8+ T cell proliferation and intracellular TNF-production. A CD39 inhibitor significantly restored proliferation and TNF-producing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RA patients, indicating that B cells from untreated RA patients conserved CD39-mediated regulatory function. Good responder patients to therapy (R-RA) exhibited an increased CD39 but not CD73 expression on B cells after treatment, while most of the non-responder (NR) patients showed a reduction in ectoenzyme expression. The positive changes of CD39 expression on B cells exhibited a negative correlation with disease activity and rheumatoid factor levels. Our results suggest modulating the ectoenzymes/ADO pathway as a potential therapy target for improving the course of RA. B cells from patients with Rheumatoid Arthritis (RA) have similar CD39 and CD73 expression to B cells from healthy controls (HC). After a positive response to therapy, B cells exhibit an increase in CD39, but not in CD73, expression and consequently higher capacity to hydrolyze eATP and to suppress CD4+ T cell proliferation and TNF production.
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影响因子：
13.6
作者：
Antonioli L;Pacher P;Vizi ES;Haskó G
通讯作者：
Haskó G
影响因子：
8.7
作者：
Allard B;Longhi MS;Robson SC;Stagg J
通讯作者：
Stagg J
DOI：
10.1038/nrrheum.2016.178
发表时间：
2017-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
82.9
作者：
Mascanfroni, Ivan D.;Takenaka, Maisa C.;Yeste, Ada;Patel, Bonny;Wu, Yan;Kenison, Jessica E.;Siddiqui, Shafiuddin;Basso, Alexandre S.;Otterbein, Leo E.;Pardoll, Drew M.;Pan, Fan;Priel, Avner;Clish, Clary B.;Robson, Simon C.;Quintana, Francisco J.
通讯作者：
Quintana, Francisco J.
DOI：
10.1161/atvbaha.111.226837
发表时间：
2012-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Linden J;Cekic C
通讯作者：
Cekic C