Ledderose Carola, Junger Wolfgang G
Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States.
Front Immunol. 2020 Sep 29;11:549889. doi: 10.3389/fimmu.2020.549889. eCollection 2020.
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.
细胞内ATP是为许多细胞过程提供能量的通用能量载体。然而，免疫细胞也可将其一部分ATP释放到细胞外空间。在那里，ATP激活嘌呤能受体，介导细胞功能起始、调节和终止所需的自分泌和旁分泌信号事件。线粒体通过产生并释放ATP来参与这些过程。在此，我们总结了线粒体与嘌呤能信号传导之间协同相互作用对T细胞功能的调节作用。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免疫防御不可或缺。然而，它们也是一个致命弱点，可使宿主易受感染和炎症性疾病影响。缺氧和线粒体功能障碍会削弱调节T细胞的嘌呤能信号传导机制，而炎症和组织损伤会使全身ATP水平过高，从而扭曲自分泌嘌呤能信号传导并损害T细胞功能。更好地理解调节T细胞的代谢和嘌呤能信号传导机制可能会带来诊断和治疗感染性和炎症性疾病的新策略。
