State Key Laboratory of Optometry, Ophthalmology, and Vision Science, The Affiliated Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Purinergic Signal. 2023 Mar;19(1):135-144. doi: 10.1007/s11302-022-09847-5. Epub 2022 Feb 15.
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 A receptor (AR) 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 AR was present at low density in the CP. The RNA-seq analysis revealed that the AR 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 AR 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, AR signaling regulates the CP permeability. Thus, AR 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.
脉络丛（CP）是调节外周免疫细胞进入中枢神经系统的关键门户之一。然而，维持其门户活性的神经调节机制尚不完全清楚。在这里，我们确定腺苷 A 受体（AR）活性是 CP 门户在生理条件下活动的调节信号。与紧密关闭的 CP 门户相关联，我们发现 CP 中的 AR 密度较低。RNA-seq 分析显示，AR 拮抗剂 KW6002 影响 CP 中细胞黏附分子（CAMs）途径和细胞对 IFN-γ的反应的表达。此外，CP 中 AR 信号的阻断或激活分别导致淋巴细胞迁移决定因素的表达减少和增加，以及紧密连接（TJ）的破坏。此外，AR 信号调节 CP 的通透性。因此，CP 中的 AR 活性可能成为重塑中枢神经系统免疫平衡的治疗靶点，这对神经免疫性疾病的治疗具有重要意义。
