Adenosine A 2A receptor controls the gateway of the choroid plexus
Adenosine A 2A receptor controls the gateway of the choroid plexus
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腺苷 A 2A 受体控制脉络丛的门户
DOI：
10.1007/s11302-022-09847-5
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发表时间：
--
影响因子：
3.5
通讯作者：
Wu Zheng
中科院分区：
文献类型：
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作者：
Mengqian Ye;Mengru Wang;Yijia Feng;Huiping Shang;Yuwen Yang;Lanxin Hu;Muran Wang;Serhii Vakal;Xiangxiang Lin;Jiangfan Chen;Wu Zheng
脉络丛（CP）是调节外周免疫细胞进入CNS的关键门户之一。然而，维持其网关活动的神经调节机制尚未完全了解。在这里，我们确定腺苷A2 A受体（A2 AR）的活动作为一个调节信号的活动CP网关在生理条件下。在与一个紧密关闭的CP网关，我们发现，A2 AR是目前在CP低密度。RNA-seq分析显示A2 AR拮抗剂KW 6002影响CP中细胞粘附分子（CAM）通路的表达和细胞对IFN-γ的反应。此外，阻断或激活CP中的A2 AR信号传导分别导致淋巴细胞运输决定簇的表达减少和增加以及紧密连接（TJ）的破坏。此外，A2 AR信号调节CP渗透性。因此，CP中的A2 AR活性可以作为重塑CNS中免疫稳态的治疗靶标，其对神经免疫学病症的治疗具有意义。
The choroid plexus (CP) is one of the key gateways regulating the entry of peripheral immune cells into the CNS. However, the neuromodulatory mechanisms of maintaining its gateway activity are not fully understood. Here, we identified adenosine A2Areceptor (A2AR) activity as a regulatory signal for the activity of CP gateway under physiological conditions. In association with a tightly closed CP gateway, we found that A2AR was present at low density in the CP. The RNA-seq analysis revealed that the A2AR antagonist KW6002 affected the expression of the cell adhesion molecules’ (CAMs) pathway and cell response to IFN-γ in the CP. Furthermore, blocking or activating A2AR signaling in the CP resulted in a decreased and an increased, respectively, expression of lymphocyte trafficking determinants and disruption of the tight junctions (TJs). Furthermore, A2AR signaling regulates the CP permeability. Thus, A2AR activity in the CP may serve as a therapeutic target for remodeling the immune homeostasis in the CNS with implications for the treatment of neuroimmunological disorders.