Extracellular adenosine reversibly inhibits the activation of human regulatory T cells and negatively influences the achievement of the operational tolerance in liver transplantation.
Extracellular adenosine reversibly inhibits the activation of human regulatory T cells and negatively influences the achievement of the operational tolerance in liver transplantation.
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DOI：
10.1111/ajt.15023
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Pons JA
中科院分区：
文献类型：
--
作者：
Baroja-Mazo A;Revilla-Nuin B;de Bejar Á;Martínez-Alarcón L;Herrero JI;El-Tayeb A;Müller CE;Aparicio P;Pelegrín P;Pons JA
在移植中人工诱导耐受的力量正在增强。在小鼠中，已经提出了细胞外腺苷（eADO）对调节性（Teff）和效应性（Teffs）T细胞的不同作用：抑制Teffs和诱导Teff。本研究的目的是分析细胞外核苷酸在人T细胞中的作用，此外，研究CD 39和CD 73外核苷酸酶和随后的腺苷信号通过腺苷2受体（A2 R）在诱导肝移植后的临床耐受的影响。细胞外核苷酸在人T细胞中的作用通过用分离的T细胞进行的体外实验来分析。此外，17例肝移植患者参加了免疫抑制停药试验，并比较了耐受和非耐受患者之间CD 39-CD 73-A2 R轴的差异。与小鼠相反，在存在eADO的情况下，人Teff的活化与Teff类似地被抑制。此外，表达的酶负责的ADO，腺苷脱氨酶（ADA）的降解，是更高的耐受患者相对于非耐受组沿着免疫抑制剂的撤药。我们的数据支持的想法，eADO信号及其降解可能在复杂的系统中发挥作用的调节肝移植耐受。
The artificial induction of tolerance in transplantation is gaining strength. In mice, a differential role of extracellular adenosine (eADO) for regulatory (Tregs) and effector (Teffs) T cells has been proposed: inhibiting Teffs and inducing Tregs. The aim of this study was to analyze the action of extracellular nucleotides in human T cells, and moreover, examine the influence of CD39 and CD73 ectonucleotidases and subsequent adenosine signaling through adenosine 2 receptor (A2R) in the induction of clinical tolerance after liver transplantation. The action of extracellular nucleotides in human T cells was analyzed by in vitro experiments with isolated T cells. Additionally, 17 liver transplant patients were enrolled in an immunosuppression withdrawal trial, and the differences in the CD39-CD73-A2R axis were compared between tolerant and non-tolerant patients. In contrast to the mice, the activation of human Tregs was inhibited similarly to Teffs in the presence of eADO. Moreover, the expression of the enzyme responsible for the degradation of ADO, adenosine deaminase (ADA), was higher in tolerant patients with respect to the non-tolerant group along the immunosuppression withdrawal. Our data support the idea that eADO signaling and its degradation may play a role in the complex system of regulation of liver transplantation tolerance.
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影响因子：
5.5
作者：
Bodor, Josef;Fehervari, Zoltan;Sakaguchi, Shimon
通讯作者：
Sakaguchi, Shimon
影响因子：
20.3
作者：
Sauer, Aisha V.;Brigida, Immacolata;Aiuti, Alessandro
通讯作者：
Aiuti, Alessandro
肝移植的耐受性：生物标志物和临床相关性。
影响因子：
4.3
作者：
Baroja-Mazo A;Revilla-Nuin B;Parrilla P;Martínez-Alarcón L;Ramírez P;Pons JA
通讯作者：
Pons JA
影响因子：
7.3
作者：
Ohta A;Kini R;Ohta A;Subramanian M;Madasu M;Sitkovsky M
通讯作者：
Sitkovsky M
影响因子：
7.3
作者：
El-Tayeb, Ali;Iqbal, Jamshed;Mueller, Christa E.
通讯作者：
Mueller, Christa E.