Regulatory T cells with a defect in inhibition on co-stimulation deteriorated primary biliary cholangitis.
Regulatory T cells with a defect in inhibition on co-stimulation deteriorated primary biliary cholangitis.
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调节性 T 细胞在抑制共刺激方面存在缺陷，导致原发性胆汁性胆管炎恶化。
DOI：
10.18632/oncotarget.22658
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发表时间：
2017-12-12
期刊：
影响因子：
--
通讯作者：
Diao H
中科院分区：
文献类型：
--
作者：
Chen J;Hou X;Jia H;Cui G;Wu Z;Wang L;Lu C;Wu W;Wei Y;Uede T;Li L;Lian Z;Diao H
调节性T细胞（Regulatory T cells，TCFs）在原发性胆管炎（Primary biliary cholangitis，PBC）的发生、发展过程中起着不可或缺的作用。虽然TGFAP可以在体内和体外模型中使共刺激正常化，但TGFAP是否以及如何在PBC中介导这些作用尚不清楚。本研究主要探讨TbR在PBC中的定量和功能特征。PBC患者外周血T淋巴细胞的数量、比例及白细胞介素（IL）-10的产生均显著低于健康对照组（HC）。PBC患者循环和肝脏共刺激分子CD 86的表达明显高于HC。CD 1c+细胞表面CD 86的表达与T淋巴细胞比例呈负相关。CD 86/Treg比值与马约风险评分呈正相关。体外实验表明，PBC患者外周血CD 1c+细胞表达CD 86的抑制作用明显减弱。PBC患者自身抗体可促进CD 1c+细胞表面CD 86的表达和肝星状细胞转化生长因子-β的产生。总的来说，在存在自身抗体的情况下，TcR对共刺激表达的抑制作用下降，这可能与PBC相关的胆管损伤和纤维化有关。这表明维持共刺激和TcR的平衡可能对PBC有益。
Regulatory T cells (Tregs) play an indispensable role in the progression of primary biliary cholangitis (PBC). Although Tregs could normalize costimulation in in vivo and in vitro models, it is obscure whether and how Tregs mediate these effects in PBC. Herein we focused on the quantitative and functional characteristics of Tregs in PBC. The number and proportion of Tregs, and the production of interleukin (IL)-10 were all significantly less in the PBC patients than in the healthy controls (HCs). In addition, compared to the HCs, the costimulatory CD86 of the circulation and liver were significantly higher in the patients with PBC. CD86 expression on CD1c+ cells negatively correlated with the proportion of Tregs. There was also a positive correlation between mayo risk score and the ratio of CD86/Treg. In vitro experiments showed that inhibition of CD86 expression on CD1c+ cells by Tregs was significantly weakened in the PBC patients. Furthermore, the autoantibodies from the PBC patients could promote CD86 expression on CD1c+ cells and transforming growth factor-β production by human hepatic stellate cells. Overall, Tregs declined in inhibition on co-stimulation expression in the presence of autoantibodies, which could be associated to PBC-related bile duct injury and fibrosis. This indicated that maintenance of balance of co-stimulation and Tregs could be beneficial for PBC.
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影响因子：
29.4
作者：
Feng T;Cao AT;Weaver CT;Elson CO;Cong Y
通讯作者：
Cong Y
影响因子：
4.4
作者：
Misra, N;Bayry, J;Kaveri, SV
通讯作者：
Kaveri, SV
揭示成红细胞岛中巨噬细胞的异质性。
影响因子：
7.3
作者：
Seu KG;Papoin J;Fessler R;Hom J;Huang G;Mohandas N;Blanc L;Kalfa TA
通讯作者：
Kalfa TA
影响因子：
13.5
作者：
Lan, RY;Cheng, C;Gershwin, ME
通讯作者：
Gershwin, ME
DOI：
10.1084/jem.182.4.1045
发表时间：
1995-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Orange JS;Wang B;Terhorst C;Biron CA
通讯作者：
Biron CA