ZAP70型
免疫系统
细胞生物学
信号转导
免疫检查点
功能(生物学)
癌症研究
生物
免疫学
T细胞
抗原提呈细胞
免疫疗法
作者
Xinhui Hui,Min Xue,Yaojun Ren,Yiran Chen,Xuenan Chen,Muhammad Asad Farooq,Yuzhou Ji,Weirong Zhan,Yunhe Huang,Bingtan Du,Jie Yao,Yixin Duan,Wenzheng Jiang
出处
期刊:Science Advances
[American Association for the Advancement of Science]
日期:2025-03-05
卷期号:11 (10)
标识
DOI:10.1126/sciadv.adr9395
摘要
As a member of the proton-sensing GPCR receptors, GPR132 plays a crucial role in regulating immune cell functions, but the mechanism by which GPR132 affects natural killer (NK) cells has not yet been reported. Here, RNA-seq displayed that the expression of GPR132 was reduced in activated NK cells, and the proportion of mature NK cells in GPR132-/- mice was substantially increased compared to WT mice, with stronger anti-melanoma capabilities. Further investigation indicates that GPR132-deficient NK92 cells expressed more GzmB and IFN-γ and exhibited stronger cytotoxicity. Mechanically, GPR132 regulates NK cell function through the CSK/ZAP70/NF-κB signaling axis. Down-regulation of GPR132 weakens the inhibition of NK cell function by lactate, thereby enhancing the functional execution of CAR-NK cells against colorectal cancer. These results highlight the previously unrecognized role of GPR132 in the regulation of NK cell function and that inhibition of GPR132 provided an updated insight for NK cell therapy.
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