Purinergic Control of T Cell Activation by ATP Released Through Pannexin-1 Hemichannels
Purinergic Control of T Cell Activation by ATP Released Through Pannexin-1 Hemichannels
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DOI：
10.1126/scisignal.1160583
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发表时间：
2008-09-30
影响因子：
7.3
通讯作者：
Grassi, Fabio
中科院分区：
文献类型：
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作者：
Schenk, Ursula;Westendorf, Astrid M.;Grassi, Fabio
T 细胞受体 (TCR) 刺激导致 Ca2+ 流入，由线粒体缓冲并促进三磷酸腺苷 (ATP) 合成。我们发现，活化的 T 细胞通过 pannexin-1 半通道释放 ATP，激活嘌呤能 P2X 受体 (P2XR)，以维持丝裂原激活蛋白激酶 (MAPK) 信号传导。 P2XR拮抗剂，例如氧化ATP（oATP），可以减弱受刺激T细胞中MAPK的激活，但不影响激活T细胞转录因子核因子的核转位，从而促进T细胞无反应性。体内给予 oATP 可以阻断抗胰岛 TCR 转基因 T 细胞介导的糖尿病发作，并损害炎症性肠病中致结肠炎 T 细胞的发育。因此，ATP 释放和信号传导的药理学抑制可能有益于治疗 T 细胞介导的炎症性疾病。
T cell receptor (TCR) stimulation results in the influx of Ca2+, which is buffered by mitochondria and promotes adenosine triphosphate (ATP) synthesis. We found that ATP released from activated T cells through pannexin-1 hemichannels activated purinergic P2X receptors (P2XRs) to sustain mitogen-activated protein kinase (MAPK) signaling. P2XR antagonists, such as oxidized ATP (oATP), blunted MAPK activation in stimulated T cells, but did not affect the nuclear translocation of the transcription factor nuclear factor of activated T cells, thus promoting T cell anergy. In vivo administration of oATP blocked the onset of diabetes mediated by anti-islet TCR transgenic T cells and impaired the development of colitogenic T cells in inflammatory bowel disease. Thus, pharmacological inhibition of ATP release and signaling could be beneficial in treating T cell-mediated inflammatory diseases.