Mitochondria Synergize With P2 Receptors to Regulate Human T Cell Function.
Mitochondria Synergize With P2 Receptors to Regulate Human T Cell Function.
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DOI：
10.3389/fimmu.2020.549889
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发表时间：
2020
影响因子：
7.3
通讯作者：
Junger WG
中科院分区：
文献类型：
--
作者：
Ledderose C;Junger WG
细胞内ATP是一种通用的能量载体，为许多细胞过程提供燃料。然而，免疫细胞也可以释放一部分ATP到细胞外空间。在那里，ATP激活嘌呤能受体，介导细胞功能启动、调节和终止所需的自分泌和旁分泌信号事件。线粒体通过产生释放的ATP来促进这些过程。在这里，我们总结了线粒体和嘌呤信号之间的协同作用，调节T细胞功能。具体而言，我们讨论了线粒体如何与P2X1，P2X4和P2Y11受体相互作用，以调节T细胞代谢，细胞迁移和抗原识别。这些线粒体和嘌呤能信号传导机制对于宿主的免疫防御是不可或缺的。然而，它们也代表了一个致命弱点，可以使宿主容易感染和炎症性疾病。缺氧和线粒体功能障碍使调节T细胞的嘌呤能信号传导机制减少，而炎症和组织损伤产生过量的全身ATP水平，其扭曲自分泌嘌呤能信号传导并损害T细胞功能。对调节T细胞的代谢和嘌呤能信号传导机制的更好理解可能会导致诊断和治疗感染性和炎症性疾病的新策略。
Intracellular ATP is the universal energy carrier that fuels many cellular processes. However, immune cells can also release a portion of their ATP into the extracellular space. There, ATP activates purinergic receptors that mediate autocrine and paracrine signaling events needed for the initiation, modulation, and termination of cell functions. Mitochondria contribute to these processes by producing ATP that is released. Here, we summarize the synergistic interplay between mitochondria and purinergic signaling that regulates T cell functions. Specifically, we discuss how mitochondria interact with P2X1, P2X4, and P2Y11 receptors to regulate T cell metabolism, cell migration, and antigen recognition. These mitochondrial and purinergic signaling mechanisms are indispensable for host immune defense. However, they also represent an Achilles heel that can render the host susceptible to infections and inflammatory disorders. Hypoxia and mitochondrial dysfunction deflate the purinergic signaling mechanisms that regulate T cells, while inflammation and tissue damage generate excessive systemic ATP levels that distort autocrine purinergic signaling and impair T cell function. An improved understanding of the metabolic and purinergic signaling mechanisms that regulate T cells may lead to novel strategies for the diagnosis and treatment of infectious and inflammatory diseases.
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