TY - JOUR
T1 - Adenosine A2A receptor controls the gateway of the choroid plexus
AU - Ye, Mengqian
AU - Wang, Mengru
AU - Feng, Yijia
AU - Shang, Huiping
AU - Yang, Yuwen
AU - Hu, Lanxin
AU - Wang, Muran
AU - Vakal, Serhii
AU - Lin, Xiangxiang
AU - Chen, Jiangfan
AU - Zheng, Wu
N1 - Funding Information:
This study was supported by the National Natural Science Foundation of China (Grant No. 31800903, 81630040) and the National Key Research and Development Program of China (Grant No. 2016YFC1306600, 2016YFC1306602).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature B.V.
PY - 2022
Y1 - 2022
N2 - 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 A2A receptor (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.
AB - 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 A2A receptor (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.
KW - Adenosine A receptors
KW - Cell adhesion
KW - CGS21680
KW - Choroid plexus
KW - KW6002
KW - Tight junctions
UR - http://www.scopus.com/inward/record.url?scp=85124772891&partnerID=8YFLogxK
U2 - 10.1007/s11302-022-09847-5
DO - 10.1007/s11302-022-09847-5
M3 - Article
C2 - 35167016
AN - SCOPUS:85124772891
SN - 1573-9538
JO - Purinergic Signalling
JF - Purinergic Signalling
ER -