The purinergic receptor P2Y11 choreographs the polarization, mitochondrial metabolism, and migration of T lymphocytes.
The purinergic receptor P2Y11 choreographs the polarization, mitochondrial metabolism, and migration of T lymphocytes.
复制标题
DOI：
10.1126/scisignal.aba3300
复制
发表时间：
2020-09-29
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;Bromberger S;Slubowski CJ;Sueyoshi K;Aytan D;Shen Y;Junger WG
T细胞必须迁移到遇到抗原呈递细胞并执行它们在宿主防御中的作用。在这里，我们发现自分泌刺激嘌呤能受体P2Y11调节人CD4 T细胞的迁移。P2Y11受体从极化细胞的前部重新分布到后部，在那里它们触发细胞内cAMP/PKA信号，减弱后部的线粒体代谢。细胞前部P2Y11受体的缺失导致线粒体代谢热点和局部ATP产生，刺激前部P2X4受体、Ca2+内流和假足突出。P2Y11受体的这种调节功能依赖于它们的亚细胞再分配和细胞ATP释放的自分泌刺激，并受到不加区分的全局刺激的干扰。我们的结论是，过量的细胞外ATP，如在炎症、败血症和癌症中发生的ATP，破坏了这种自分泌反馈机制，导致T细胞迁移缺陷，T细胞功能受损，以及宿主免疫防御丧失。
T cells must migrate to encounter antigen-presenting cells and carry out their roles in host defense. Here, we showed that autocrine stimulation of the purinergic receptor P2Y11 regulate the migration of human CD4 T cells. P2Y11 receptors redistributed from the front to the back of polarized cells where they trigger intracellular cAMP/PKA signals that attenuate mitochondrial metabolism at the back. The absence of P2Y11 receptors at the front of cells resulted in hotspots of mitochondrial metabolism and localized ATP production that stimulated P2X4 receptors, Ca2+ influx, and pseudopod protrusion at the front. This regulatory function of P2Y11 receptors depended on their subcellular redistribution and autocrine stimulation by cellular ATP release and was perturbed by indiscriminate global stimulation. We conclude that excessive extracellular ATP, such as that which occurs in inflammation, sepsis, and cancer, disrupts this autocrine feedback mechanism, which results in defective T cell migration, impaired T cell function, and loss of host immune defense.
登录
查看更多内容
炎症过程中的核苷酸信号传导。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.8
作者：
Haskó G;Antonioli L;Cronstein BN
通讯作者：
Cronstein BN
影响因子：
2.9
作者：
Glancy, Brian;Balaban, Robert S.
通讯作者：
Balaban, Robert S.
DOI：
10.1007/5584_2017_89
发表时间：
2017-01-01
期刊：
PROTEIN REVIEWS, VOL 19
影响因子：
--
作者：
Kennedy, Charles
通讯作者：
Kennedy, Charles
影响因子：
5.5
作者：
Clark，Adam A.;Nurmukhambetova，Saule;Lees，Jason R.
通讯作者：
Lees，Jason R.