Effect of the purinergic inhibitor oxidized ATP in a model of islet allograft rejection.
Effect of the purinergic inhibitor oxidized ATP in a model of islet allograft rejection.
复制标题
葡聚糖抑制剂在同种异体移植排斥模型中氧化ATP的影响。
作者：
Vergani A;Fotino C;D'Addio F;Tezza S;Podetta M;Gatti F;Chin M;Bassi R;Molano RD;Corradi D;Gatti R;Ferrero ME;Secchi A;Grassi F;Ricordi C;Sayegh MH;Maffi P;Pileggi A;Fiorina P
淋巴细胞亲离子嘌呤能P2 X受体（P2 X1 R-P2 X7 R，或P2 XRs）感知细胞损伤-活化过程中释放的ATP，从而调节T细胞活化。我们的目的是明确P2 XRs在胰岛移植排斥反应中的作用，并建立一种新的抗P2 XRs策略来实现长期胰岛移植功能。我们的数据表明，P2 X1 R和P2 X7 R诱导的胰岛同种异体移植物浸润细胞，只有P2 X7 R是越来越多的表达在同种免疫反应，P2 X1 R增强在同种异体和同基因移植。体内短期P2 X7 R靶向（使用高碘酸氧化ATP [oATP]）延迟胰岛移植排斥反应，降低Th 1/Th 17细胞的频率，并诱导对供体抗原的低反应性。oATP处理的小鼠显示保留的胰岛移植物，具有减少的Th 1转录物。P2 X7 R靶向和雷帕霉素协同诱导80%的移植小鼠的长期胰岛功能，并导致受体免疫系统的重塑。使用oATP的体外P2 X7 R靶向降低了T细胞活化并减少了Th 1/Th 17细胞因子的产生。与对照组相比，从长期胰岛移植患者中获得的外周血单个核细胞显示P2 X7 R + CD 4 + T细胞的百分比增加。oATP治疗的有益效果揭示了嘌呤能系统在胰岛移植排斥反应中的作用，靶向P2 X7 R是诱导长期胰岛移植功能的新策略。
The lymphocytic ionotropic purinergic P2X receptors (P2X1R-P2X7R, or P2XRs) sense ATP released during cell damage-activation, thus regulating T-cell activation. We aim to define the role of P2XRs during islet allograft rejection and to establish a novel anti-P2XRs strategy to achieve long-term islet allograft function. Our data demonstrate that P2X1R and P2X7R are induced in islet allograft-infiltrating cells, that only P2X7R is increasingly expressed during alloimmune response, and that P2X1R is augmented in both allogeneic and syngeneic transplantation. In vivo short-term P2X7R targeting (using periodate-oxidized ATP [oATP]) delays islet allograft rejection, reduces the frequency of Th1/Th17 cells, and induces hyporesponsiveness toward donor antigens. oATP-treated mice displayed preserved islet grafts with reduced Th1 transcripts. P2X7R targeting and rapamycin synergized in inducing long-term islet function in 80% of transplanted mice and resulted in reshaping of the recipient immune system. In vitro P2X7R targeting using oATP reduced T-cell activation and diminished Th1/Th17 cytokine production. Peripheral blood mononuclear cells obtained from long-term islet-transplanted patients showed an increased percentage of P2X7R+CD4+ T cells compared with controls. The beneficial effects of oATP treatment revealed a role for the purinergic system in islet allograft rejection, and the targeting of P2X7R is a novel strategy to induce long-term islet allograft function.
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影响因子：
7.7
作者：
Fiorina, Paolo;Jurewicz, Mollie;Abdi, Reza
通讯作者：
Abdi, Reza
影响因子：
6.2
作者：
Fiorina, P;Folli, F;Secchi, A
通讯作者：
Secchi, A
影响因子：
16.2
作者：
Bloomgarden, ZT
通讯作者：
Bloomgarden, ZT
影响因子：
64.8
作者：
通讯作者：
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DOI：
10.1038/nri2938
发表时间：
2011-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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